Reduced Expression of Brain-Enriched microRNAs in Glioblastomas Permits Targeted Regulation of a Cell Death Gene

In the paper

“In fact, individual miRNAs are predicted to target as many as 200 different mRNAs [12].”

What the sources say

• Disputed

  The Results and Discussion section estimates 438 ± 60 or 497 ± 49 conserved targets per miRNA family, rather than an upper figure of 200 mRNAs. The widespread scope of conserved targeting section also estimates 292 ± 18 targets per broadly conserved miRNA even when considering only 7–8mer sites. (LLM, conf=0.84)

  Checked by a reasoning model — may be wrong.

  cites [12] RC Friedman, 2009, Most mammalian mRNAs are conserved targets of microRNAs., Genome Res sourceExperimental — accuracy not yet measured

In the 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].”

What the sources say

• Partly supported

  The Results section reports that miR-124 and miR-137 promote neuronal differentiation in adult neural stem cells. Its expression table also compares miR-128a with non-neoplastic brain tissue, but the paper does not show that miR-128 regulates neuronal differentiation, maturation, or survival, or establish that all three are enriched in the brain relative to other tissues. Page numbers are unavailable in our copy. (LLM, conf=0.87)

  cites [15] J Silber, 2008, miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells., BMC Med sourceExperimental — accuracy not yet measured
• Partly supported

  The Results and discussion section lists miR-128, miR-124a/b, and miR-137 among miRNAs expressed in the brain. It also reports that miR-128 and miR-124a/b increase during neuronal differentiation in cultured cells. The paper suggests a possible role in neuronal differentiation, but does not show that these miRNAs regulate differentiation, maturation, or survival; it does not report miR-137 increasing in that experiment. Page numbers are unavailable in our copy. (LLM, conf=0.90)

  cites [20] LF Sempere, 2004, Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation., Genome Biol sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [21] J Godlewski, 2010, MicroRNAs and glioblastoma; the stem cell connection., Cell Death Differ source
• Supported

  The Abstract identifies miR-128 as brain-enriched. The Discussion links miR-128 to differentiation and reports that its forced expression produces effects associated with retinoic-acid-induced differentiation, including reduced migration. In this multi-citation sentence, this paper supports the miR-128 portion of the claim. (LLM, conf=0.86)

  cites [22] C Evangelisti, 2009, MiR-128 up-regulation inhibits Reelin and DCX expression and reduces neuroblastoma cell motility and invasiveness., FASEB J source
• Partly supported

  The Results report that miR-124a is highly enriched in the brain, and the Results and Discussion link it to suppression of nonneuronal transcripts and maintenance of neuronal identity. The passages found for miR-128 and miR-137 do not address their brain enrichment or roles in neuronal differentiation, maturation, or survival, so this source supports only the miR-124 portion of the claim. Page numbers are unavailable in our copy. (LLM, conf=0.88)

  cites [23] C Conaco, 2006, Reciprocal actions of REST and a microRNA promote neuronal identity., Proc Natl Acad Sci U S A sourceExperimental — accuracy not yet measured

In the paper

“the pro-oncogenic miRNA miR-10b is upregulated in glioblastomas and has recently been shown to be a significant contributor to tumor growth in vivo [9], [17].”

What the sources say

• ?Not checked — no full text of the sourcecites [9] SA Ciafre, 2005, Extensive modulation of a set of microRNAs in primary glioblastoma., Biochem Biophys Res Commun source
• Supported

  The Introduction says miR-10b is strongly upregulated in glioma. The Abstract reports that inhibiting miR-10b significantly reduced tumor growth in a mouse model of human glioma, supporting its contribution to growth in vivo. (LLM, conf=0.94)

  cites [17] G Gabriely, 2011, Human Glioma Growth Is Controlled by MicroRNA-10b., Cancer Res source

In the paper

“Previous miRNA profiling studies, based on miRNA microarrays and PCR arrays, have revealed a number of miRNAs to be altered in gliomas [9], [14]–[16].”

What the sources say

• ?Not checked — no full text of the sourcecites [9] SA Ciafre, 2005, Extensive modulation of a set of microRNAs in primary glioblastoma., Biochem Biophys Res Commun source
• ?Not checked — no full text of the sourcecites [14] J Godlewski, 2008, Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal., Cancer Res source
• Supported

  The Results section reports that this study used quantitative RT-PCR to profile miRNAs in gliomas and found altered expression, including changes consistent with earlier studies. The Discussion identifies microarrays as the technology used in previous GBM profiling studies, supporting the claim's description of both approaches. (LLM, conf=0.91)

  cites [15] J Silber, 2008, miR-124 and miR-137 inhibit proliferation of glioblastoma multiforme cells and induce differentiation of brain tumor stem cells., BMC Med source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [16] JT Huse, 2009, The PTEN-regulating microRNA miR-26a is amplified in high-grade glioma and facilitates gliomagenesis in vivo., Genes Dev source

In the paper

“Furthermore, several of these miRNA variants (miR-376 family members, miR-411, miR-379, and miR-320a) have previously been described in deep sequencing studies performed on human brain [36], [37], and therefore, are not specific to glioblastoma.”

What the sources say

• Partly supported

  In Results and Discussion (‘Expression of edited mature miRNAs’; page not provided), the paper identifies edited miR-379-5p and miR-411-5p in human brain and discusses edited miR-376 family members. This supports those variants occurring outside glioblastoma, but our copy does not identify a miR-320a variant. The paper describes its own approach as targeted cloning, not deep sequencing; its discussion of a deep-sequencing survey concerns a separate study. (LLM, conf=0.88)

  cites [36] Y Kawahara, 2008, Frequency and fate of microRNA editing in human brain., Nucleic Acids Res sourceExperimental — accuracy not yet measured
• Partly supported

  The Results section ('miRNA variability is ubiquitous in control and HD brain samples'; page not available) reports variants of miR-376a/b/c, miR-411, and miR-379 in human brain samples, supporting the point that those variants are not specific to glioblastoma. It discusses miR-320b and miR-320c, however, rather than the claimed miR-320a; searching our copy for miR-320a did not establish that part of the list. (LLM, conf=0.86)

  cites [37] E Marti, A myriad of miRNA variants in control and Huntington's disease brain regions detected by massively parallel sequencing., Nucleic Acids Res sourceExperimental — accuracy not yet measured

In the paper

“Similarly, CREB-induced miR-132 and miR-212, which share seed sequence homology, promote dendritic outgrowth from newborn neurons [55] and can target methyl CpG binding protein 2 (MeCP2), a regulator of neuroplasticity [56], [57].”

What the sources say

• Partly supported

  The Results state that miR-132 and miR-212 have identical seed sequences, and the Discussion concludes that miR-132 mediates dendritic outgrowth in newborn hippocampal neurons. But the Results identify miR-132, not miR-212, as active in those neurons, so the paper does not support attributing that effect to both. The MeCP2 statement has separate citations [56] and [57], rather than this paper's citation [55]. (LLM, conf=0.88)

  cites [55] ST Magill, microRNA-132 regulates dendritic growth and arborization of newborn neurons in the adult hippocampus., Proc Natl Acad Sci U S A sourceExperimental — accuracy not yet measured
• ?Not checked — no full text of the sourcecites [56] ME Klein, 2007, Homeostatic regulation of MeCP2 expression by a CREB-induced microRNA., Nat Neurosci source
• Supported

  The Results section (‘miR-212 inhibits striatal MeCP2 expression’) reports that miR-212 reduces MeCP2 expression and notes that miR-132 regulates a MeCP2 transcript. The Discussion (‘MeCP2 acts through homeostatic interactions with miR-212’) likewise describes interactions between MeCP2 and both miRNAs. The dendritic-outgrowth clause is attached to a different citation, [55], and is not judged here. (LLM, conf=0.91)

  cites [57] HI Im, MeCP2 controls BDNF expression and cocaine intake through homeostatic interactions with microRNA-212., Nat Neurosci source

In the 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].”

What the sources say

• Partly supported

  In Results and discussion (‘Diverse miRNA expression patterns in mammalian organs’), the paper lists both miR-7 and miR-124 among brain-expressed miRNAs. In ‘A subset of brain-expressed miRNAs is induced in retinoic acid-treated EC cells’, it reports that miR-124 increases during neuronal differentiation, but miR-7 is not among the induced miRNAs. The paper does not directly compare expression in neural progenitors and neurons, so it does not establish that full contrast for both miRNAs. (LLM, conf=0.87)

  cites [20] LF Sempere, 2004, Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation., Genome Biol sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (page not available) report that miR-124a was barely detectable in dividing cortical progenitors, appeared in mature cortical neurons, and was associated with neuronal differentiation. The passages found do not establish the corresponding expression pattern or differentiation role for miR-7; a search for miR-7 found no passage addressing it. (LLM, conf=0.88)

  cites [23] C Conaco, 2006, Reciprocal actions of REST and a microRNA promote neuronal identity., Proc Natl Acad Sci U S A sourceExperimental — accuracy not yet measured
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [54] X Li, 2005, A microRNA mediates EGF receptor signaling and promotes photoreceptor differentiation in the Drosophila eye., Cell source

In the paper

“which could have dramatic consequences on mRNA targeting [25], [27].”

What the sources say

• ?Not checked — no full text of the sourcecites [25] Y Kawahara, 2007, Redirection of silencing targets by adenosine-to-inosine editing of miRNAs., Science source
• Partly supported

  The Results and Discussion (page not provided) describe variation in miRNA 5′ ends and suggest that different seed sequences may affect binding to target RNAs. This supports the possibility of targeting consequences from 5′-end polymorphisms. The passages do not address A-to-I editing or its consequences for targeting. (LLM, conf=0.84)

  cites [27] H Seitz, 2008, Argonaute loading improves the 5′ precision of both MicroRNAs and their miRNA strands in flies., Curr Biol sourceExperimental — accuracy not yet measured

In the paper

“we identified over 400 different cellular pre-miRNAs”

In the paper

“No known viral miRNAs were detected in any of the samples analyzed.”

• Also stated in: § Small RNA deep sequencing reveals differences in human miRNA expression patterns · plain

  “No viral miRNAs were detected in any of the samples analyzed.”

In the paper

“Between 1.8 and 4.9 million reads were obtained per sample (Table S1)”

In the paper

“Among the 16,305,416 mapped reads, 484 mature human miRNAs/miRNA*s were represented at least 10 times (Table S2).”

In the paper

“the sequence length distributions showed peaks at ∼22–23 nt for each sample, corresponding to the average length of a mature miRNA (Fig. S1).”

In the paper

“under the regulation of a miRNA, miR-128, that was found to be enriched in non-tumor brain tissue yet down-regulated in glioblastomas”

In the paper

“Both the ectopic expression of miR-128 in glioblastoma cells and the natural, endogenous level of miR-128 expression seen in neuronal cells indeed limited cell death when compared to control glioblastoma cells.”

In the paper

“We also observed high read counts for miR-21, amongst other miRNAs, in all glioblastoma samples compared to non-tumor samples, congruent with previous studies showing that this miRNA is highly up-regulated in glioblastoma (Table S4) [5], [9], [14], [15]; however, there was variability in the values for miR-21 across the samples and thus, the miRNA did not meet the final FDR selection criteria.”

What the sources say

• ?Not checked — no full text of the sourcecites [5] JA Chan, 2005, MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells., Cancer Res source
• ?Not checked — no full text of the sourcecites [9] SA Ciafre, 2005, Extensive modulation of a set of microRNAs in primary glioblastoma., Biochem Biophys Res Commun source
• ?Not checked — no full text of the sourcecites [14] J Godlewski, 2008, Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal., Cancer Res source

In the paper

“These 5′ nucleotide variations were observed in all nine sequencing libraries, and with the exception of miR-124-3p, there was no correlation of 5′ end variability and miRNA expression differences in tumors versus non-tumor samples (Table S4, S7, and S8).”

In the paper

“A to G substitutions for each of the miRNAs were found in both the glioblastoma and non-tumor brain tissue libraries, and there were no significant differences in the averaged abundance of edited miRNAs between the two sample types (Table 1).”

In the paper

“We therefore expanded our cut-off to p<0.1 to include 21 significantly dysregulated miRNAs, 17 of which were down-regulated in glioblastoma.”

In the paper

“Interestingly, the dominant form of miR-324-3p was consistent with the miRNA sequence reported in miRBase; however, in non-tumor brain, we observed a significant number of reads mapping to a miR-324-3p isoform that was two nucleotides longer at the 5′ end (Table S7).”

In the paper

“Several of the miRNAs down-regulated in glioblastoma (including miR-124-3p and miR-323-3p) exhibited 5′ truncations or additions while one up-regulated miRNA, miR-10b-5p, exhibited 5′ variations (Table S8).”

In the paper

“Congruent with previous studies, A to G changes occurred in >60% of the reads for members of the miR-376 family (miR-376a, b, and c) at nucleotide position six of the mature miRNA sequence (Table 1, Fig. S3A) [36].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [36] Y Kawahara, 2008, Frequency and fate of microRNA editing in human brain., Nucleic Acids Res source

In the paper

“The 3p miRNAs for miR-330 and miR-204 were preferentially detected in non-tumor brain tissue, while the 5p miRNAs were preferentially detected in glioblastomas (Table S7; Fig. S3B).”

In the paper

“the data presented here provide a comprehensive analysis of the miRNA signature in glioblastoma”

In the paper

“At the highest dose, 200 µg/mL GCV, ∼70% of HSV-TK-expressing cells were killed (Fig. 4C & D).”

In the paper

“we report a number of miRNA sequence variants that are expressed in the brain.”

In the paper

“A to G substitutions also occurred in the seed region of miR-320 family members; however, these miRNAs were unusual in that several positions (two, three, and four) exhibited nucleotide substitutions (Fig. S3A and data not shown).”

In the paper

“Two major isoforms were observed for both miR-30a-3p and miR-330-3p.”

In the paper

“miR-212, miR-218, and miR-379, amongst others, also exhibited lower read counts in glioblastoma compared to non-tumor brain tissue (Table S4), but did not meet the final FDR selection criteria.”

In the paper

“We also noted A to G substitutions at nucleotide position four for miR-381 and position five for miR-411, miR-200b, and miR-379 (Table 1, Fig. S3A).”

In the paper

“however, in the majority of the glioblastoma libraries, the miRNAs expressed from the 3p arms were under-represented while miR-30a-5p and miR-330-5p were enriched (Fig. S3B).”

In the paper

“Similarly, miR-30a-5p was enriched in glioblastomas while in non-tumor brain tissue, miR-30a-5p and miR-30a-3p were expressed at similar levels (Table S7; Fig. S3B).”

In the paper

“Primer extension analysis confirmed enhanced expression of miR-21 (Fig. 2A) and decreased expression of miR-128, miR-124, and miR-132 (Fig. 2B) in glioblastomas compared to non-tumor brain tissue samples.”

In the paper

“we also observed down-regulation of miR-124, miR-128, miR-132, and miR-7”

In the paper

“Our sequencing data reveal that miR-128 has an invariant sequence and does not exhibit post-transcriptional editing or significant 5′ end variation.”

In the paper

“Glioblastoma is associated with a number of mutations at the genomic level including mutations in the PTEN tumor suppressor and amplification of the gene encoding the epidermal growth factor receptor (EGFR) [3], [4].”

What the sources say

• ?Not checked — no full text of the sourcecites [3] PY Wen, 2008, Malignant gliomas in adults., N Engl J Med source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [4] H Ohgaki, 2009, Genetic alterations and signaling pathways in the evolution of gliomas., Cancer Sci source

In the paper

“In addition, we identified variation in the 5′ ends of several miRNAs expressed in glioblastomas as well as editing in the seed region, which should modulate the mRNA targets bound by these miRNAs.”

In the paper

“Similar approaches have been used to selectively prevent transgene expression in hematopoetic cells and other cell types [28]–[31].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [28] EJ Kelly, 2009, MicroRNAs and the regulation of vector tropism., Mol Ther source
• ?Not checked — no full text of the sourcecites [29] BD Brown, 2009, Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications., Nat Rev Genet source
• ?Not checked — no full text of the sourcecites [30] BD Brown, 2006, Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer., Nat Med source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [31] C Wu, 2009, Combinatorial control of suicide gene expression by tissue-specific promoter and microRNA regulation for cancer therapy., Mol Ther source

In the paper

“Of note, miR-7 can directly repress expression of EGFR, which is often amplified at the genetic level and/or over-expressed at the protein level in gliomas [19].”

What the sources say

• ?Not checked — no full text of the sourcecites [19] B Kefas, 2008, microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma., Cancer Res source

In the paper

“More recently, dysregulated microRNA (miRNA) expression, such as over-expression of the anti-apoptotic miRNA miR-21, has been linked to tumor pathogenesis [5].”

What the sources say

• ?Not checked — no full text of the sourcecites [5] JA Chan, 2005, MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells., Cancer Res source

In the paper

“Moreover, single pre-miRNA precursors occasionally give rise to not only the dominant, miRNA strand, but also a less highly expressed passenger or star strand, which may also be able to regulate mRNA expression [13].”

What the sources say

• Not checked yetcites [13] JS Yang, 2011, Widespread regulatory activity of vertebrate microRNA* species., RNA source

In the paper

“To validate results from our deep sequencing experiments, we selected four differentially expressed miRNAs for further analysis: miR-21, miR-128, miR-124, and miR-132.”

In the paper

“These data suggest that 5′ end polymorphisms can reflect fluctuations in strand dominance and presumably, reflect variations in Drosha processing of the primary miRNA transcript.”

In the paper

“Such changes may indicate post-transcriptional processing differences—for instance, the absence or presence of a factor in glial versus non-glial cells that perturbs miRNA strand selection.”

In the paper

“demonstrating that high-throughput sequencing can be an effective method for profiling miRNA expression.”

In the paper

“Compared to microarray and PCR-based profiling platforms, which detect a pre-determined set of miRNAs, high-throughput sequencing provides a more complete picture of the miRNAs expressed in a given sample and is not restricted in the number of individual miRNAs that can be detected.”

In the paper

“an approach that could be readily extended to cancers of other organs.”

In the paper

“None of the samples were post-mortem.”

In the paper

“HSV-TK-based lentiviral vectors are currently in phase I/II clinical trials for glioblastoma treatment [39], [40].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [39] KJ Pulkkanen, 2005, Gene therapy for malignant glioma: current clinical status., Mol Ther source
• ?Not checked — no full text of the sourcecites [40] NG Rainov, 2003, Gene therapy for human malignant brain tumors., Cancer J source

In the paper

“One post-transcriptional miRNA modification is enzymatic editing of the dsRNA primary miRNA transcript by ADAR (adenosine deaminase acting on RNA) which results in the conversion of an adenosine (A) to an inosine (I) [24].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [24] K Nishikura, 2010, Functions and regulation of RNA editing by ADAR deaminases., Annu Rev Biochem source

In the paper

“De-identified tissues were used for all studies and the data were analyzed anonymously.”

In the paper

“A to I conversions can influence loading of miRNAs into RISC [34] and also alter the targeting capacity of a miRNA, especially if the editing occurs within the miRNA seed region [24], [25].”

What the sources say

• Not checked yetcites [34] DS Schwarz, 2003, Asymmetry in the assembly of the RNAi enzyme complex., Cell source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [24] K Nishikura, 2010, Functions and regulation of RNA editing by ADAR deaminases., Annu Rev Biochem source
• ?Not checked — no full text of the sourcecites [25] Y Kawahara, 2007, Redirection of silencing targets by adenosine-to-inosine editing of miRNAs., Science source

In the paper

“many of which (miR-128, miR-124, miR-7, miR-132, miR-139) are consistently dysregulated in not only gliomas but also other brain cancers including medulloblastomas and neuroblastomas [33].”

What the sources say

• ?Not checked — no full text of the sourcecites [33] JC Pang, 2009, Oncogenic role of microRNAs in brain tumors., Acta Neuropathol source

In the paper

“449 mature miRNAs and miRNAs* were identified using a filter of RPKM score >1 to normalize read counts between different libraries and by considering only those miRNAs occurring in at least two out of three non-tumor brain libraries or 50% of the glioblastoma libraries (Table S4).”

In the paper

“we used the miRNAkey pipeline, implementing the SeqEM option to account for reads mapping to multiple miRNAs [32].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [32] R Ronen, 2010, miRNAkey: a software for microRNA deep sequencing analysis., Bioinformatics source

In the paper

“It is hypothesized that glioblastomas, like other cancers such as leukemia [51], arise and are maintained by a population of progenitor cells with stem-like characteristics including the ability to self-renew for unlimited proliferation [21], [52], [53].”

What the sources say

• ?Not checked — no full text of the sourcecites [51] BJ Huntly, 2005, Leukaemia stem cells and the evolution of cancer-stem-cell research., Nat Rev Cancer source
• ?Not checked — no full text of the sourcecites [21] J Godlewski, 2010, MicroRNAs and glioblastoma; the stem cell connection., Cell Death Differ source
• ?Not checked — no full text of the sourcecites [52] SK Singh, 2004, Cancer stem cells in nervous system tumors., Oncogene source

In the paper

“Finally, miR-128, which is also abundantly expressed in neurons, has been shown to target the Bmi-1 stem cell renewal factor [14].”

What the sources say

• ?Not checked — no full text of the sourcecites [14] J Godlewski, 2008, Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal., Cancer Res source

In the paper

“When cultured in the presence of all-trans retinoic acid (ATRA), SH-SY5Y cells undergo morphological changes, differentiate into neuron-like cells, express neuronal markers, and up-regulate a number of brain-specific miRNAs [42], [43].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [42] S Meseguer, MicroRNAs-10a and -10b Contribute to Retinoic Acid-induced Differentiation of Neuroblastoma Cells and Target the Alternative Splicing Regulatory Factor SFRS1 (SF2/ASF)., J Biol Chem source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [43] MT Le, 2009, MicroRNA-125b promotes neuronal differentiation in human cells by repressing multiple targets., Mol Cell Biol source

In the paper

“Additionally, single nucleotide changes have been shown to affect miRNA expression, processing, and/or function [35].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [35] Y Kawahara, 2007, RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex., EMBO Rep source

In the paper

“The use of tissue-specific miRNAs to regulate transgene expression for therapeutic applications has been investigated in multiple cell types, including lymphoid and myeloid cells, muscle cells, liver cells, and brain cells [28]–[31].”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [28] EJ Kelly, 2009, MicroRNAs and the regulation of vector tropism., Mol Ther source
• ?Not checked — no full text of the sourcecites [29] BD Brown, 2009, Exploiting and antagonizing microRNA regulation for therapeutic and experimental applications., Nat Rev Genet source
• ?Not checked — no full text of the sourcecites [30] BD Brown, 2006, Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer., Nat Med source
• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [31] C Wu, 2009, Combinatorial control of suicide gene expression by tissue-specific promoter and microRNA regulation for cancer therapy., Mol Ther source

In the paper

“This vector showed the same therapeutic efficacy in glioblastoma U87 cells as a control HSV-TK vector lacking artificial miRNA target sites, but when introduced into human astrocytes, which express the three selected miRNAs, showed restricted HSV-TK expression, leading to an increase in cell viability.”

What the sources say

• Not checked yet

  Checked before — its earlier verdict is held back until a new check runs.

  cites [31] C Wu, 2009, Combinatorial control of suicide gene expression by tissue-specific promoter and microRNA regulation for cancer therapy., Mol Ther source

In the paper

“A single A to I conversion in the seed of miR-376a-5p, for example, redirects the edited miRNA to a new set of mRNA targets [25].”

What the sources say

• ?Not checked — no full text of the sourcecites [25] Y Kawahara, 2007, Redirection of silencing targets by adenosine-to-inosine editing of miRNAs., Science source

In the paper

“reduced expression of miR-128 is not specific to just glioblastomas as this miRNA is also down-regulated in other brain cancers [33].”

What the sources say

• ?Not checked — no full text of the sourcecites [33] JC Pang, 2009, Oncogenic role of microRNAs in brain tumors., Acta Neuropathol source

In the paper

“Given the much broader dynamic range of deep sequencing compared to finite platforms such as miRNA microarrays or real-time PCR arrays, we therefore used a FDR cut-off of p<0.1.”

In the 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.”

What the sources say

• Not checked yetcites [20] LF Sempere, 2004, Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation., Genome Biol source
• ?Not checked — no full text of the sourcecites [21] J Godlewski, 2010, MicroRNAs and glioblastoma; the stem cell connection., Cell Death Differ source

In the paper

“clearly additional miRNAs identified here are dysregulated in glioblastoma (Fig. 1, Tables S4 and S6).”