The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index; 20 of the 42 sources its claims cite were checked for support.
Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation
Open accessAbstract
BACKGROUND: The microRNAs (miRNAs) are an extensive class of small noncoding RNAs (18 to 25 nucleotides) with probable roles in the regulation of gene expression. In Caenorhabditis elegans, lin-4 and let-7 miRNAs control the timing of fate specification of neuronal and hypodermal cells during larval development. lin-4, let-7 and other miRNA genes are conserved in mammals, and their potential functions in mammalian development are under active study. RESULTS: In order to identify mammalian miRNAs that might function in development, we characterized the expression of 119 previously reported miRNAs in adult organs from mouse and human using northern blot analysis. Of these, 30 miRNAs were specifically expressed or greatly enriched in a particular organ (brain, lung, liver or skeletal muscle). This suggests organ- or tissue-specific functions for miRNAs. To test if any of the 66 brain-expressed miRNAs were present in neurons, embryonal carcinoma cells were treated with all-trans-retinoic acid to promote neuronal differentiation. A total of 19 brain-expressed miRNAs (including lin-4 and let-7 orthologs) were coordinately upregulated in both human and mouse embryonal carcinoma cells during neuronal differentiation. The mammalian ortholog of C. elegans lin-28, which is downregulated by lin-4 in worms via 3' untranslated region binding, was also repressed during neuronal differentiation of mammalian embryonal carcinoma cells. Mammalian lin-28 messenger RNAs contain conserved predicted binding sites in their 3' untranslated regions for neuron-expressed miR-125b (a lin-4 ortholog), let-7a, and miR-218. CONCLUSIONS: The identification of a subset of brain-expressed miRNAs whose expression behavior is conserved in both mouse and human differentiating neurons implicates these miRNAs in mammalian neuronal development or function.
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TL;DR
Northern blot profiling of 119 mammalian microRNAs in adult mouse and human organs identified conserved organ-specific and organ-enriched expression, including a prominent brain-expressed subset. Several brain-expressed miRNAs were induced during retinoic-acid-driven neuronal differentiation of mouse P19 and human NT2/D1 embryonal carcinoma cells, and LIN-28 was downregulated with conserved predicted miRNA binding sites.
Key findings
- Of 119 miRNAs analyzed, 92 were previously cloned and 27 were computationally predicted; 21 of 27 predicted miRNAs were detected by northern blot. Seventeen miRNAs were detected exclusively in one mouse organ, including seven brain-specific miRNAs (miR-9, -124a, -124b, -135, -153, -183, -219), six lung-specific, two spleen-specific, one liver-specific, and one heart-specific miRNA. Among 75 miRNAs detected in two or more mouse organs, 14 were enriched at least two-fold in one organ, including seven brain-enriched miRNAs (miR-9*, -125a, -125b, -128, -132, -137, -139), three skeletal muscle-enriched, two kidney-enriched, and one spleen-enriched miRNA.
- Hierarchical clustering identified at least six major groups of miRNAs with similar expression profiles, including a group of 17 miRNAs expressed in mouse and human brain; about 50% of expressed miRNAs were assigned to a specific or restricted set of organs.
- Retinoic acid treatment induced 19 miRNAs in both P19 and NT2/D1 cells, including four brain-specific, four brain-enriched, and 11 brain-nonenriched miRNAs; induction in P19 cells typically occurred by day four after RA treatment.
- LIN-28 protein levels began to decrease around day five and almost disappeared by day eight in P19 cells; in NT2/D1 cells, LIN-28 decreased slightly by day 14 and was still detectable at day 21. This kinetics paralleled upregulation of miR-125b, let-7a, and miR-218, and mouse and human Lin-28 mRNAs contain conserved predicted binding sites for these miRNAs.
Methods
- Northern analysis of 119 miRNAs using StarFire probes on total RNA from adult mouse organs (six-week-old C57BL/6 mice, pooled organs from two to four mice) and human organs, plus P19 and NT2/D1 embryonal carcinoma cells treated with 1 μM and 10 μM retinoic acid, respectively.
- Northern blot signals were quantified with ImageQuant and clustered with GeneTraffic 6.2 using Pearson hierarchical clustering; western analysis was used to measure LIN-28 protein.
- miRNA::target mRNA predictions were made by testing 20-nucleotide 3′ UTR segments for RNA secondary structure with the RNAfold program of the Vienna RNA package, applying binding, free-energy, and mouse-human conservation filters and a numerical scoring formula.
Limitations
- Stated: some cloned and predicted miRNAs were not detected, possibly because of low expression, expression limited to a small number of cells or a narrow developmental window, or lack of expression in the organs examined; the organ panel did not include all organs and tissues from which miRNAs were cloned, and human kidney, lung, and spleen were not examined.
- Stated: glial expression was not directly examined, so the possibility that RA-induced miRNAs were also expressed in glial cells could not be eliminated; a luciferase reporter fused to the mouse Lin-28 3′ UTR was not downregulated in differentiating P19 cells, and endogenous Lin-28 mRNA decreased, suggesting that repression of native Lin-28 may be largely transcriptional and that miRNA regulation may be auxiliary.
- Evident: the miRNA target predictions are computational and were not experimentally validated by loss-of-function experiments; the paper notes that miRNA loss-of-function experiments in these EC cells could prove useful for understanding their regulatory contribution.
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Claims the paper makes
37 Own result · 19 Own interpretation · 11 No full text of the sources · 6 Partly supported · 4 Own method · 3 Supported · 3 Not checked yet · 2 Supported so far · 2 Sources not found · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Mouse P19 and human NTera-2 clone D1 (NT2/D1) are EC cells that differentiate into neurons upon RA-treatment [39-41].”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > A subset of brain-expressed miRNAs is induced in retinoic acid-treated EC cells
What the sources say
- Not checked — no full text of the sourcecites [39] Jones-Villeneuve EM, Rudnicki MA, Harris JF, McBurney MW: Retinoic acid-induced neural differentiation of embryonal carcinoma cells.Mol Cell Biol 1983, 3:2271–2279. source
- Partly supportedcites [40] Jones-Villeneuve EM, McBurney MW, Rogers KA, Kalnins VI: Retinoic acid induces embryonal carcinoma cells to differentiate into neurons and glial cells.J Cell Biol 1982, 94:253–262. sourceExperimental — accuracy not yet measured
The Abstract (p. 253) identifies P19 as a murine embryonal carcinoma line and reports that retinoic acid-treated P19 cultures produced neurons. The paper does not address the human NTera-2 clone D1 (NT2/D1), so it supports only the P19 part of the cited sentence. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [41] Andrews PW: Retinoic acid induces neuronal differentiation of a cloned human embryonal carcinoma cell linein vitro.Dev Biol 1984, 103:285–293. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“miRNAs that were abundantly cloned in a particular organ, such as miR-135 and miR-153 from brain [2], were exclusively detected by northern analysis in mouse and human brain.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
What the sources say
- Partly supportedcites [2] Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T: Identification of tissue-specific microRNAs from mouse.Curr Biol 2002, 12:735–739. sourceExperimental — accuracy not yet measured
The passage on neural tissue distribution (section labeled Abstract; page unavailable) reports cloning miRNAs from mouse brain, supporting the general point about organ-specific cloning. It names miR-124 as abundant and lists other brain-cloned miRNAs, but does not identify miR-135 or miR-153 as brain clones. The citation is attached to the cloning clause; the subsequent Northern-analysis result is not attributed to this source. (LLM, conf=0.82)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Our characterization of organ expression of miRNAs correlates with the organ(s) from which these miRNAS were originally cloned [2,3].”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
What the sources say
- Supportedcites [2] Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T: Identification of tissue-specific microRNAs from mouse.Curr Biol 2002, 12:735–739. source
The paper reports cloning miRNAs from specific mouse tissues and finding corresponding tissue-enriched expression. In the supplied Abstract passages, miRNAs cloned from brain tissues were shown by Northern blotting to be predominantly brain-specific; miR-1 was abundant in heart and miR-122 in liver. This supports the citation’s role in identifying the organs from which the miRNAs were cloned, without attributing the citing authors’ own characterization to the source. (LLM, conf=0.90)
- Supportedcites [3] Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T: New microRNAs from mouse and human.RNA 2003, 9:175–179. source
The Results and Discussion table identifies the tissues from which individual miRNAs were cloned, supplying the original-cloning information cited here. The correlation with organ expression is the citing authors’ own characterization, not a result attributed to this source. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“We observed that the same series of miRNAs was upregulated in EC cells upon RA-treatment.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > A subset of brain-expressed miRNAs is induced in retinoic acid-treated EC cells
What the sources say
- Supportedcites [17] Krichevsky AM, King KS, Donahue CP, Khrapko K, Kosik KS: A microRNA array reveals extensive regulation of microRNAs during brain development.RNA 2003, 9:1274–1281. source
The paper’s “miRNA expression during corticogenesis” section reports developmentally regulated miRNAs in rat forebrain, including a group with a shared pattern of upregulation from E12 to E21. The EC-cell response to RA treatment is the citing authors’ own observation, not a finding attributed to Krichevsky et al. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Myc and Cyclin D1 are well-characterized cases of genes repressed by RA-treatment at the levels of transcription and translation in differentiating neurons [47,48].”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > LIN-28 could be a potential target for miRNA regulation in embryonal carcinomas
What the sources say
- Not checked — no full text of the sourcecites [47] Miller WH Jr, Moy D, Li A, Grippo JF, Dmitrovsky E: Retinoic acid induces down-regulation of several growth factors and proto-oncogenes in a human embryonal cancer cell line.Oncogene 1990, 5:511–517.
- Partly supportedcites [48] Spinella MJ, Freemantle SJ, Sekula D, Chang JH, Christie AJ, Dmitrovsky E: Retinoic acid promotes ubiquitination and proteolysis of cyclin D1 during induced tumor cell differentiation.J Biol Chem 1999, 274:22013–22018. sourceExperimental — accuracy not yet measured
The Results report that RA lowers cyclin D1 protein in NT2/D1 human embryonal carcinoma cells before terminal neuronal differentiation. The Discussion attributes the decline largely to ubiquitin-dependent degradation and says transcriptional regulation may also contribute; it does not establish repression at both transcriptional and translational levels. This paper does not establish the claim for Myc or for differentiating neurons. (LLM, conf=0.88)
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“we observed some discrepancies between our expression profiling by northern analysis and expression profiling by cloning [2,3]. This is particularly so for certain less-abundant miRNAs - those that were represented in size-selected RNA libraries by three or fewer copies.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
What the sources say
- Partly supportedcites [2] Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T: Identification of tissue-specific microRNAs from mouse.Curr Biol 2002, 12:735–739. sourceExperimental — accuracy not yet measured
The paper’s Abstract says low-abundance miRNAs can be identified by cloning even when Northern blot analysis does not detect them, and gives miR-1 in liver and midbrain as an example. It does not establish the citing authors’ threshold of three or fewer copies in size-selected libraries; its mention of three miR-1 copies refers to copies or polymorphic alleles, not library counts. The citing authors’ own observed discrepancies are not attributed to this source. (LLM, conf=0.86)
- Supportedcites [3] Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T: New microRNAs from mouse and human.RNA 2003, 9:175–179. source
The Results and Discussion describe cloning miRNAs from mouse tissues and a human cell line, and Table 1 reports clone counts by tissue—supporting the citation’s use for cloning-based expression profiles. The discrepancies with northern analysis are the citing authors’ own observation, not a finding attributed to this source. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“This study confirms the expression of previously cloned miRNAs [1-3,9,10]”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
What the sources say
- Not checked — no full text of the sourcecites [1] Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T: Identification of novel genes coding for small expressed RNAs.Science 2001, 294:853–858. source
- Supportedcites [2] Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T: Identification of tissue-specific microRNAs from mouse.Curr Biol 2002, 12:735–739. source
The paper reports cloning miRNAs from adult mouse tissues and detecting their expression. In the passage labeled Abstract (page unavailable), it specifically reports expression of miR-1, a previously described miRNA, in heart, liver, and midbrain. This supports the claim that the study confirms expression of previously cloned miRNAs. (LLM, conf=0.85)
- Supportedcites [3] Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T: New microRNAs from mouse and human.RNA 2003, 9:175–179. source
The Results and Discussion (page not provided) report that 91% of the miRNAs cloned from the sampled mouse tissues and human cells were previously identified miRNAs. Recovering those miRNAs in these samples supports the claim that the study confirmed their expression. (LLM, conf=0.92)
- Supportedcites [9] Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G: miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs.Genes Dev 2002, 16:720–728. source
In “Numerous miRNAs, derived from novel genes, associate with the Gemin3-Gemin4-eIF2C2 complex” (page not supplied), the paper reports that nine miRNAs it identified were identical to miRNAs previously reported by Lagos-Quintana et al. It also says Northern blots confirmed expression of the identified miRNAs in HeLa cells. (LLM, conf=0.91)
- Supportedcites [10] Dostie J, Mourelatos Z, Yang M, Sharma A, Dreyfuss G: Numerous microRNPs in neuronal cells containing novel microRNAs.RNA 2003, 9:180–186. source
In “Identification and characterization of miRNAs,” the paper reports finding several miRNAs previously identified from total RNA in neuronal-cell miRNPs. This supports the claim that previously cloned miRNAs were detected again. (LLM, conf=0.91)
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed a strong induction of miR-9/miR-9* expression in P19 cells.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > A subset of brain-expressed miRNAs is induced in retinoic acid-treated EC cells
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Yet, we did not detect downregulation, in differentiating P19 cells, of a luciferase reporter gene fused to the mouse Lin-28 3' UTR and driven by a cytomegalovirus (CMV) or thymidine kinase (TK) promoter (data not shown).”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > LIN-28 could be a potential target for miRNA regulation in embryonal carcinomas
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“All of the indicated mouse brain-, liver- and heart-specific miRNAs were also detected in the human counterpart organs (miRNA expression was not examined in human kidney, lung or spleen), with the exception of miR-183 in the human brain.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 28
- Probably not a substantial claim. 13
- The quote only partly states this claim. 1
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“The panel of organs that we tested in our study did not include all the organs and tissues that miRNAs were cloned from [1-3,9,10], and thus some organ-specific or organ-enriched miRNAs may be expressed in additional organs or tissues.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
What the sources say
- Not checked — no full text of the sourcecites [1] Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T: Identification of novel genes coding for small expressed RNAs.Science 2001, 294:853–858. source
- Supportedcites [2] Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T: Identification of tissue-specific microRNAs from mouse.Curr Biol 2002, 12:735–739. source
The paper reports cloning miRNAs from several mouse tissues, including heart, liver, spleen, colon and brain (Abstract; no page given). It also finds low-level miR-1 expression in liver and midbrain despite its predominance in heart. The statement about which organs the citing authors tested describes their own study, not this source. (LLM, conf=0.88)
- Supportedcites [3] Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T: New microRNAs from mouse and human.RNA 2003, 9:175–179. source
The Results and Discussion section identifies this paper as a study that cloned miRNAs from multiple mouse tissues, including lung, kidney, skin, testis, ovary, thymus, spinal cord, and eye. The citing authors’ statement about the limits of their own organ panel is their inference; this source supports the cited premise about tissues used for cloning. (LLM, conf=0.90)
- Supportedcites [9] Mourelatos Z, Dostie J, Paushkin S, Sharma A, Charroux B, Abel L, Rappsilber J, Mann M, Dreyfuss G: miRNPs: a novel class of ribonucleoproteins containing numerous microRNAs.Genes Dev 2002, 16:720–728. source
The cited paper is used as an example of a source from which miRNAs were cloned, not as evidence about the citing authors’ organ panel or their inference about expression elsewhere. Its “Immunoprecipitations and cloning of miRNAs” section describes cloning miRNAs from HeLa cell lysate (page not available in our copy). (LLM, conf=0.86)
- Supportedcites [10] Dostie J, Mourelatos Z, Yang M, Sharma A, Dreyfuss G: Numerous microRNPs in neuronal cells containing novel microRNAs.RNA 2003, 9:180–186. source
The citation identifies a source from which miRNAs were cloned; it does not attribute the citing authors’ organ panel or their inference about expression in additional tissues to this paper. In “Identification and characterization of miRNAs” (page not supplied), the source reports sequencing clones from Weri and MN-1 neuronal cells. (LLM, conf=0.89)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Notably, mir-142s/mir-142as are located in the junction of the t(8;17) chromosomal rearrangement. This translocation fuses Bcl3 and Myc genes, thus resulting in an aggressive B-cell leukemia [2,37].”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Some miRNAs are associated with chromosomal rearrangements
What the sources say
- Partly supportedcites [2] Lagos-Quintana M, Rauhut R, Yalcin A, Meyer J, Lendeckel W, Tuschl T: Identification of tissue-specific microRNAs from mouse.Curr Biol 2002, 12:735–739. sourceExperimental — accuracy not yet measured
The passage labeled Abstract (page unavailable) places mir-142 at the t(8;17) breakpoint and says the translocation causes aggressive B-cell leukemia through upregulation of MYC. It does not say that the translocation fuses Bcl3 and MYC; instead, it describes translocated MYC immediately downstream of the miR-142 precursor. (LLM, conf=0.88)
- Supportedcites [37] Gauwerky CE, Huebner K, Isobe M, Nowell PC, Croce CM: Activation of MYC in a masked t(8;17) translocation results in an aggressive B-cell leukemia.Proc Natl Acad Sci USA 1989, 86:8867–8871. source
The citation is attached to the second sentence. The paper reports that the t(8;17) translocation joined MYC to BCL3 regulatory elements and links the resulting MYC expression to aggressive B-cell leukemia (opening summary and Discussion; page numbers not supplied). It does not describe a fusion of the genes’ coding sequences. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“lin-4 RNA binds to the 3' UTR of target mRNAs, including lin-28, and inhibits their translation [27,45].”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > LIN-28 could be a potential target for miRNA regulation in embryonal carcinomas
What the sources say
- Not checked — no full text of the sourcecites [27] Olsen PH, Ambros V: The lin-4 regulatory RNA controls developmental timing inCaenorhabditis elegansby blocking LIN-14 protein synthesis after the initiation of translation.Dev Biol 1999, 216:671–680. source
- Partly supportedcites [45] Moss EG, Lee RC, Ambros V: The cold shock domain protein LIN-28 controls developmental timing inC. elegansand is regulated by the lin-4 RNA.Cell 1997, 88:637–646. sourceExperimental — accuracy not yet measured
The Discussion (page unavailable) reports that lin-4 RNA and a complementary element in the lin-28 3′ UTR are necessary for down-regulation of lin-28. The section headed “Regulation of lin-28 Expression by lin-4 RNA” (page unavailable) describes complementarity as predicted; it does not establish physical binding to lin-28 or directly demonstrate inhibition of its translation, rather than posttranscriptional down-regulation. (LLM, conf=0.84)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Upregulation of lin-4 RNA during the first larval stage (L1) triggers the progression from early (L1) to late (L2-L3) fate programs [24].”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > LIN-28 could be a potential target for miRNA regulation in embryonal carcinomas
What the sources say
- Supportedcites [24] Feinbaum R, Ambros V: The timing of lin-4 RNA accumulation controls the timing of postembryonic developmental events inCaenorhabditis elegans.Dev Biol 1999, 210:87–95. source
The Discussion says that lin-4S RNA accumulation during L1 determines when LIN-14 is down-regulated and thereby specifies the timing and sequence of larval developmental programs. It also reports that premature lin-4 expression produces L2 cell-lineage patterns in L1; the Results report precocious L3-specific patterns in L2. Page numbers are not available in the supplied copy. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“They included four of the brain-specific (miR-9, -124a, -124b, -135), four of the brain-enriched (miR-9*, -125a, -125b, -128), and 11 of the brain-nonenriched (let-7a, let-7b, miR-30a, -30b, -30c, -30e, -98, -100, 103-1, -156, -218).”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > A subset of brain-expressed miRNAs is induced in retinoic acid-treated EC cells
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: miRNAs with evolutionarily conserved roles in neurons should be induced during neuronal differentiation of both mouse and human EC cells.
- Rests on an assumption: The induction of miRNAs in RA-treated EC cells reflects their expression during neuronal differentiation in vivo.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed a high percentage of brain-specific and brain-enriched miRNAs compared to miRNAs enriched or specific to other organs (14 out of 30 miRNAs in mouse), and an overall prevalence of miRNAs expressed in the brain (66 out of 90 miRNAs in mouse).”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > A subset of brain-expressed miRNAs is induced in retinoic acid-treated EC cells
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“mir-208, which is expressed in the mouse and human heart, resides in an intron of human cardiac α-myosin heavy chain.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > miRNAs can be expressed from long transcripts
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“miR-9/miR-9* and miR-145 were cloned in cDNA libraries from human hypothalamus (gi|28436750) and trachea (gi|21752921), respectively.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > miRNAs can be expressed from long transcripts
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“these included: seven brain-enriched miRNAs (miR-9*, -125a, -125b, -128, -132, -137, -139), three skeletal muscle-enriched miRNAs (miR-1d, -133, -206), two kidney-enriched miRNAs (miR-30b, -30c), and one spleen-enriched miRNA (miR-99a)”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A similar result was observed in NT2/D1 cells; LIN-28 levels decreased slightly, typically by day 14, and were still detectable at day 21.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > LIN-28 could be a potential target for miRNA regulation in embryonal carcinomas
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A group of six miRNAs was expressed in mouse and human skeletal muscle and heart: miR-1b, -1d, -133 and -206 had elevated expression in heart and skeletal muscle with low expression in other organs and miR-143 and -208 were almost exclusively detected in heart and skeletal muscle.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed similar expression profiles for the pair of linked miRNAs, mir-194 and mir-215, and also for both members of the mir-1d~mir-133 cluster (Figure 3).”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Coordinate expression of closely linked miRNAs
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Closely linked miRNAs arranged in tandem often exhibit similar expression profiles, consistent with shared cis-regulatory elements and possibly a polycistronic precursor transcript.
None of the sources cited for this claim have been checked yet.
In the paper
“Both miR-191 and miR-214 were contained in long transcripts cloned in cDNA libraries from mouse neonate head (gi|26096865) and eyeball (gi|26094816), respectively.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > miRNAs can be expressed from long transcripts
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“LIN-28 levels began to decrease on about day five after RA-treatment, and almost disappeared by day eight, when cells reached their final state of neuronal differentiation.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > LIN-28 could be a potential target for miRNA regulation in embryonal carcinomas
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“these included: seven brain-specific miRNAs (miR-9, -124a, -124b, -135, -153, -183, -219), six lung-specific miRNAs (miR-18, -19a, -24, -32, -130, -213), two spleen-specific miRNAs (miR-189, -212), one liver-specific miRNA (miR-122a), and one heart-specific miRNA (miR-208)”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, not only the protein levels but also the RNA levels of Lin-28 decreased upon RA treatment suggesting that other factors must also mediate this process.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Conclusions
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In both mouse and human examined organs, seven miRNAs were expressed specifically in a particular organ and ten miRNAs were greatly enriched in a particular organ over all others (Figure 2).”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Conclusions
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“mir-15 and mir-16 reside on chromosome 13q14, a region associated with chronic lymphocytic leukemia (CLL) (Figure 3b).”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Some miRNAs are associated with chromosomal rearrangements
What the sources say
- Not checked — no full text of the sourcecites [36] Calin GA, Dumitru CD, Shimizu M, Bichi R, Zupo S, Noch E, Aldler H, Rattan S, Keating M, Rai K, et al.: Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia.Proc Natl Acad Sci USA 2002, 99:15524–15529. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“P19 and NT2/D1 have similar programs of neuronal differentiation, though the differentiation of P19 cells progresses more rapidly than that of NT2/D1 cells [42,43].”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > A subset of brain-expressed miRNAs is induced in retinoic acid-treated EC cells
What the sources say
- Not checked — no full text of the sourcecites [42] Bain G, Ray WJ, Yao M, Gottlieb DI: From embryonal carcinoma cells to neurons: the P19 pathway.Bioessays 1994, 16:343–348. source
- Not checked — no full text of the sourcecites [43] Andrews PW: Teratocarcinomas and human embryology: pluripotent human EC cell lines. Review article.APMIS 1998, 106:158–167. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results therefore suggest that, unlike C. elegans larval development, where lin-28 downregulation is primarily caused by translational repression by lin-4 RNA, the decline of Lin-28 during neuronal differentiation of P19 cells involves primarily transcriptional repression.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > LIN-28 could be a potential target for miRNA regulation in embryonal carcinomas
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In C. elegans, lin-4 (the ortholog of mir-125) and let-7 are engaged in a genetic pathway that controls temporal cell fates during larval development [25,26].”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > LIN-28 could be a potential target for miRNA regulation in embryonal carcinomas
What the sources say
- Not checked — no full text of the sourcecites [25] Pasquinelli AE, Ruvkun G: Control of developmental timing by microRNAs and their targets.Annu Rev Cell Dev Biol 2002, 18:495–513. source
- Not checked — no full text of the sourcecites [26] Rougvie AE: Control of developmental timing in animals.Nat Rev Genet 2001, 2:690–701. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Interestingly, LIN-28 is present in undifferentiated P19 and NT2/D1 cells, but it is not detected in neuronal or liver tissues [46].”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > LIN-28 could be a potential target for miRNA regulation in embryonal carcinomas
What the sources say
- Not checked — no full text of the sourcecites [46] Moss EG, Tang L: Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites.Dev Biol 2003, 258:432–442. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“which suggests that these clustered miRNAs probably belong to the same transcriptional unit, but accumulate differentially in vivo as a result of differences in post-transcriptional processing or stability.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Coordinate expression of closely linked miRNAs
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Only a subset of the brain-expressed miRNAs were detected in neurons derived from RA-treated EC cells suggesting that other brain-expressed miRNAs are present primarily in nonneuronal cell types such as glia. Alternatively, these other brain-expressed miRNAs may be present in neuronal subtypes not represented in differentiated neurons derived from EC cells.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > A subset of brain-expressed miRNAs is induced in retinoic acid-treated EC cells
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“An early phase of commitment to neuronal fate occurs within two days after RA-treatment for P19 and NT2/D1 cells. A later phase of terminal differentiation takes place between days five to eight in P19 cells and is delayed for more than three weeks in NT2/D1 cells [42,43].”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > A subset of brain-expressed miRNAs is induced in retinoic acid-treated EC cells
What the sources say
- Not checked — no full text of the sourcecites [42] Bain G, Ray WJ, Yao M, Gottlieb DI: From embryonal carcinoma cells to neurons: the P19 pathway.Bioessays 1994, 16:343–348. source
- Not checked — no full text of the sourcecites [43] Andrews PW: Teratocarcinomas and human embryology: pluripotent human EC cell lines. Review article.APMIS 1998, 106:158–167. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Since we did not directly examine expression of miRNAs in glial cells, we could not eliminate the possibility that RA-induced miRNAs were also expressed in glial cells.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > A subset of brain-expressed miRNAs is induced in retinoic acid-treated EC cells
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“mir-29 resides on chromosome 7q31. This FRA7G region is frequently altered in different tumor types including prostate, breast, and ovarian cancer [38].”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Some miRNAs are associated with chromosomal rearrangements
What the sources say
- Not checked — no full text of the sourcecites [38] Huang H, Qian J, Proffit J, Wilber K, Jenkins R, Smith DI: FRA7G extends over a broad region: coincidence of human endogenous retroviral sequences (HERV-H) and small polydispersed circular DNAs (spcDNA) and fragile sites.Oncogene 1998, 16:2311–2319. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Other cases of clustered miRNAs with different expression profiles, such as mir-132 and mir-212, could represent closely linked but independent transcription units.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Coordinate expression of closely linked miRNAs
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“RNA folding output generated by ViennaRNA was analyzed using the following software filters to evaluate the strength of the predicted target::miRNA interaction: at least two out of the three first and last bases of the miRNA had to be bound to the target sequence; at least 65% of the miRNA sequence had to be bound to the target sequence; the free energy (ΔG) of the binding had to be greater than -”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Materials and methods > miRNA::target mRNA predictions
What the sources say
- Not matchedcites [51] Vienna RNA package[http://www.tbi.univie.ac.at/~ivo/RNA/]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one. The quote only partly states this claim.
- Not matched
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the case of targets whose expression is primarily controlled on the translational level, miRNAs could play a primary regulatory role; in other cases, such as mammalian Lin-28, where the primary mode of regulation is transcriptional, translational repression by miRNAs could play an auxiliary, or supplementary regulatory role.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data associate miRNAs to particular organs and suggest their participation in conserved developmental or physiological pathways within these spatial domains in mouse and human.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Conclusions
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Hybridization/background ratios of ≤ 1.1 were not reported as positive signals, except when the band was readily detectable by eye (Figures 2, 5).”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Materials and methods > Data clustering
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Membranes were stripped by boiling in 0.1% SDS and re-hybridized up to five times without observing decreases in quality or intensity of radioactive signals.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Materials and methods > Northern analysis
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The scoring scheme was modeled based on the experimentally confirmed interaction between lin-4 RNA::lin-28 3' UTR in C. elegans.”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Materials and methods > miRNA::target mRNA predictions
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Closely linked miRNAs arranged in tandem often exhibit similar expression profiles, consistent with shared cis-regulatory elements and possibly a polycistronic precursor transcript.
“Closely linked miRNAs that are arranged in tandem often exhibit similar expression profiles, consistent with shared cis-regulatory elements, and possibly a polycistronic precursor transcript.”
The paper relies on this without support.
miRNAs with evolutionarily conserved roles in neurons should be induced during neuronal differentiation of both mouse and human EC cells.
“We reasoned that miRNAs with evolutionarily conserved roles in neurons should be induced during neuronal differentiation of both mouse and human EC cells.”
The paper relies on this without support.
The induction of miRNAs in RA-treated EC cells reflects their expression during neuronal differentiation in vivo.
“To determine which of brain-expressed miRNAs were associated with neuronal differentiation, we examined their expression during neuronal differentiation of EC cells.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A subset of these miRNA genes has been detected in mammalian tissues including heart, skeletal muscle, brain, lung, liver, kidney, spleen and placenta [25–31].”
From Expression of miR-15/107 Family MicroRNAs in Human Tissues and Cultured Rat Brain Cells (2014) · cites this paper as [28]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The neuronal cluster included miR-124, a miRNA that is especially abundant in neurons affirming the specificity of the methodology [20]–[22].”
From MicroRNA 146a (miR-146a) Is Over-Expressed during Prion Disease and Modulates the Innate Immune Response and the Microglial Activation State (2012) · cites this paper as [21]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The human brain has also been examined for miR expression and miR-219-5p, miR-338-5p, miR-338-3p, and members of the miR-17-92 cluster have been reported to be expressed (Barad et al., 2004; Sempere et al., 2004).”
From Regulation of miRNA 219 and miRNA Clusters 338 and 17-92 in Oligodendrocytes (2012) · cites this paper as Sempere et al., 2004
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Recent studies on the brain enriched miR-9 have revealed its importance in development and lineage commitment (Sempere et al., 2004; Krichevsky et al., 2006).”
From The Bifunctional microRNA miR-9/miR-9* Regulates REST and CoREST and Is Downregulated in Huntington's Disease (2008) · cites this paper as Sempere et al., 2004
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“miR-128, miR-124, and miR-137 are all enriched in the brain and have been shown to regulate neuronal differentiation, maturation, and/or survival [15], [20]–[23].”
From Reduced Expression of Brain-Enriched microRNAs in Glioblastomas Permits Targeted Regulation of a Cell Death Gene (2011) · cites this paper as [20]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Brain-enriched miR-124 and miR-7, for example, show poor expression in neural progenitors, but are highly expressed in neurons and have been implicated in neural differentiation [20], [23], [54].”
From Reduced Expression of Brain-Enriched microRNAs in Glioblastomas Permits Targeted Regulation of a Cell Death Gene (2011) · cites this paper as [20]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“During development, many miRNAs are expressed in neurons or show distinct expression patterns within the developing central nervous system (CNS), implying their importance in brain development and function (Krichevsky et al. 2003;Miska et al. 2004;Sempere et al. 2004;Smirnova et al. 2005;Wienholds et al. 2005).”
From MicroRNA expression in the adult mouse central nervous system (2008) · cites this paper as Sempere et al. 2004
The cited source says what the claim attributes to it.
In the citing paper
“Previous studies had instead compared the miRNA expression in whole brain tissue with the expression in other tissues of the same organism (Sempere et al., 2004;Wienholds et al., 2005) or assessed differences in miRNA expression during different stages of development of individual neural cell types (Krichevsky et al., 2003;Smirnova et al., 2005;Zhao et al., 2010).”
From Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes (2013) · cites this paper as Sempere et al., 2004
The cited source says what the claim attributes to it.
In the citing paper
“Compared with other organs, the brain has a particularly high percentage of tissue-specific and tissue-enriched miR-NAs (Lagos-Quintana et al., 2002;Kim et al., 2004;Sempere et al., 2004;Smirnova et al., 2005).”
From Comprehensive expression analyses of neural cell-type-specific miRNAs identify new determinants of the specification and maintenance of neuronal phenotypes (2013) · cites this paper as Sempere et al., 2004
In the citing paper
“Additionally, miR-128 is highly enriched in the brain as it is expressed by neurons and is induced during neuronal differentiation of embryonal carcinoma (EC) cells [20], [21], thus making it an ideal candidate to limit cell suicide gene expression.”
From Reduced Expression of Brain-Enriched microRNAs in Glioblastomas Permits Targeted Regulation of a Cell Death Gene (2011) · cites this paper as [20]
In the citing paper
“Moreover, microRNAs can re-arrange a genetic and molecular landscape in a cell-type-specific manner130 due to the strict tissue and cell-type-specific distribution and functions of microRNAs,210 meaning their targets in cancer and normal cells are different.”
From MiR-128-3p – a gray eminence of the human central nervous system (2024) · cites this paper as [210]
In the citing paper
“First, we confirmed the silencing efficacy of LNA-486 by luciferase assay on two validated targets of miR-486a/b-5p (Foxo1 and Pten) (52,53)”
From MicroRNA profiling of mouse cortical progenitors and neurons reveals miR-486-5p as a regulator of neurogenesis (2020) · cites this paper as [53]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
“A group of five miRNAs showed abundant expression across organs”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
“(let-7a, -7b, miR-30b, -30c).”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
“the levels of 14 of these were detected in a particular mouse organ at levels at least two-fold higher than in any other organ; these included: seven brain-enriched miRNAs (miR-9*, -125a, -125b, -128, -132, -137, -139), three skeletal muscle-enriched miRNAs (miR-1d, -133, -206), two kidney-enriched miRNAs (miR-30b, -30c), and one spleen-enriched miRNA (miR-99a)”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
Reported 14 · recomputed 13
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
“A group of 17 miRNAs was expressed in mouse and human brain (miR-7, -9, -9*, -124a, -124b, -125a, -125b, -128, -132, -135, -137, -139, -153, -149, -183, -190, -219)”
§ Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation > Results and discussion > Diverse miRNA expression patterns in mammalian organs
“with the exception of miR-183 in the human brain.”
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Metadata
- Authors
- Sempere, L. F., Freemantle, S., Pitha-Rowe, I., Moss, E., Dmitrovsky, E., & Ambros, V.
- Affiliations
- Dartmouth College (US)
- Corresponding author
- Ambros, Victor
- Venue
- Genome Biology
- Published
- 2004-02-16
- Volume
- 5
- Issue
- 3
- Pages
- R13-R13
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC395763
- OpenAlex
- W2138954682
- Cited by
- 1,578
- References
- 51
- Citations by year
- 2026: 13 · 2025: 33 · 2024: 36 · 2023: 39 · 2022: 55 · 2021: 68 · 2020: 56 · 2019: 62 · 2018: 65 · 2017: 62 · 2016: 78 · 2015: 89 · 2014: 106 · 2013: 108 · 2012: 90
- FWCI
- 29.01
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Genome biology (publishedVersion)
- PubMed Central (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Funders
- Lance Armstrong Foundation
- Armstrong Foundation
- National Institutes of Health
- National Cancer Institute (R01CA062275, T32CA009658, R01CA087546)
- National Institute of General Medical Sciences (R01GM034028)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- microRNA, neuronal differentiation, lin-4, let-7 microRNA, Lin28, miR-125b, miR-218, embryonal carcinoma cells, all-trans retinoic acid, 3' untranslated region, tissue-specific gene expression, neuronal development, miRNA expression profiling
- MeSH terms
- Adult, Animals, Brain, Cell Differentiation, Cell Line, Embryo, Mammalian, Humans, Genetic Linkage, Mice, Inbred C57BL, Neurons, Repressor Proteins, RNA, Messenger, Sequence Homology, Nucleic Acid, Stem Cells, Translocation, Genetic, Tretinoin, Down-Regulation, Gene Expression Regulation, Neoplastic, Carcinoma, Embryonal, Gene Expression Regulation, Developmental, Gene Expression Profiling, Caenorhabditis elegans Proteins, MicroRNAs, Cell Line, Tumor, Mice, Genes, Neoplasm
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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