Distinct MicroRNAs Expression Profile in Primary Biliary Cirrhosis and Evaluation of miR 505-3p and miR197-3p as Novel Biomarkers
Open accessAbstract
BACKGROUND AND AIMS: MicroRNAs are small endogenous RNA molecules with specific expression patterns that can serve as biomarkers for numerous diseases. However, little is known about the expression profile of serum miRNAs in PBC. METHODS: First, we employed Illumina deep sequencing for the initial screening to indicate the read numbers of miRNA expression in 10 PBC, 5 CH-C, 5 CH-B patients and 5 healthy controls. Comparing the differentially expressed miRNAs in the 4 groups, analysis of variance was performed on the number of sequence reads to evaluate the statistical significance. Hierarchical clustering was performed using an R platform and we have found candidates for specific miRNAs in the PBC patients. Second, a quantitative reverse transcription PCR validation study was conducted in 10 samples in each group. The expression levels of the selected miRNAs were presented as fold-changes (2(-ΔΔCt)). Finally, computer analysis was conducted to predict target genes and biological functions with MiRror 2.0 and DAVID v6.7. RESULTS: We obtained about 12 million 32-mer short RNA reads on average per sample and the mapping rates to miRBase were 16.60% and 81.66% to hg19. In the statistical significance testing, the expression levels of 81 miRNAs were found to be differentially expressed in the 4 groups. The heat map and hierarchical clustering demonstrated that the miRNA profiles from PBC clustered with those of CH-B, CH-C and healthy controls. Additionally, the circulating levels of hsa-miR-505-3p, 197-3p, and 500a-3p were significantly decreased in PBC compared with healthy controls and the expression levels of hsa-miR-505-3p, 139-5p and 197-3p were significantly reduced compared with the viral hepatitis group. CONCLUSIONS: Our results indicate that sera from patients with PBC have a unique miRNA expression profile and that the down-regulated expression of hsa-miR-505-3p and miR-197-3p can serve as clinical biomarkers of PBC.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
miR-505-3p is known to have a tumor suppressor role.
“miR-505-3p is one of the miR types known to have a tumor suppressor role (14)(15)(16)(17).”
From Functional interaction between miR-505-3p and miR-21 contributes to GBM suppression (2026) · cites this paper as [16]
The Discussion identifies reduced serum miR-505-3p as a potential biomarker for primary biliary cirrhosis, but does not describe it as a tumor suppressor. Searches for “miR-505-3p tumor suppressor” and “tumor suppressor cancer miR-505” found no passage addressing that role. Page numbers were not available in our copy. (LLM, conf=0.73)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Circulating microRNAs, potential biomarkers for drug-induced liver injury
Wang, K., Zhang, S., Marzolf, B., Troisch, P., Brightman, A., Hu, Z., Hood, L. E., & Galas, D. J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813371106 · Cited by 1,149 · see citing works
Primary biliary cirrhosis in monozygotic and dizygotic twins: Genetics, epigenetics, and environment
Selmi, C., Mayo, M. J., Bach, N., Ishibashi, H., Invernizzi, P., Gish, R. G., Gordon, S. C., Wright, H. I., Zweiban, B., Podda, M., et al. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.05.005 · Cited by 480 · see citing works
Nakamura, M., Nishida, N., Kawashima, M., Aiba, Y., Tanaka, A., Yasunami, M., Nakamura, H., Komori, A., Nakamuta, M., Zeniya, M., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2012.08.010 · Cited by 267 · see citing works
Self-citationNakanuma, Y., & Ohta, G. (1979) · Gastroenterology · doi:10.1016/0016-5085(79)90396-2 · Cited by 213 · see citing works
Flagged first, then by citations
Research works printed but not linked: 51
- [1]Lau NC, Lim LP, Weinstein EG, Bartel DP (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294: 858– 862. 11679671
- [2]Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294: 853– 858. 11679670
- [3]Lee RC, Ambros V (2001) An extensive class of small RNAs in Caenorhabditis elegans. Science 294: 862– 864. 11679672
- [4]Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116: 281– 297. 14744438
- [5]Chen X, Ba Y, Ma L, Cai X, Yin Y, et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Research 18: 997– 1006. 18766170
- [6]Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, et al (2005) MicroRNA expression profiles classify human cancers. Nature 435: 834– 838. 15944708
- [7]Bihrer V, Friedrich-Rust M, Kronenberger B, Forestier N, Haupenthal J, et al (2011) Serum miR-122 as a biomarker of necroinflammation in patients with chronic hepatitis C virus infection. Am J Gastroenterol 106: 1663– 1669. 21606975
- [8]Zhang Y, Jia Y, Zheng R, Guo Y, Wang Y, et al (2010) Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases. Clin Chem 56: 1830– 1838. 20930130
- [9]Cermelli S, Ruggieri A, Marrero JA, Ioannou GN, Beretta L (2011) Circulating MicroRNAs in Patients with Chronic Hepatitis C and Non-Alcoholic Fatty Liver Disease. PLoS One 6: e23937. 21886843 PMC3160337
- [10]Morita K, Taketomi A, Shirabe K, Umeda K, Kayashima H, et al (2011) Clinical significance and potential of hepatic microRNA-122 expression in hepatitis C. Liver Int 31: 474– 484. 21199296
- [11]Li LM, Hu ZB, Zhou ZX, Chen X, Liu FY, et al (2010) Serum microRNA Profiles Serve as Novel Biomarkers for HBV Infection and Diagnosis of HBV-Positive Hepatocarcinoma. Cancer Research 70: 9798– 9807. 21098710
- [13]Gershwin ME, Mackay IR, Sturgess A, Coppel RL (1987) Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recognized in primary biliary cirrhosis. J Immunol 138: 3525– 3531. 3571977
- [14]Coppel RL, McNeilage LJ, Surh CD, Van de Water J, Spithill TW, et al (1988) Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: dihydrolipoamide acetyltransferase. Proc Natl Acad Sci U S A 85: 7317– 7321. 3174635 PMC282177
- [16]Begovich AB, Klitz W, Moonsamy PV, Van de Water J, Peltz G, et al (1994) Genes within the HLA class II region confer both predisposition and resistance to primary biliary cirrhosis. Tissue Antigens 43: 71– 77. 8016844
- [17]Donaldson PT, Baragiotta A, Heneghan MA, Floreani A, Venturi C, et al (2006) HLA class II alleles, genotypes, haplotypes, and amino acids in primary biliary cirrhosis: a large-scale study. Hepatology 44: 667– 674. 16941709
- [18]Onishi S, Sakamaki T, Maeda T, Iwamura S, Tomita A, et al (1994) DNA typing of HLA class II genes; DRB1*0803 increases the susceptibility of Japanese to primary biliary cirrhosis. J Hepatol 21: 1053– 1060. 7699227
- [19]Hirschfield GM, Liu X, Xu C, Lu Y, Xie G, et al (2009) Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. N Engl J Med 360: 2544– 2555. 19458352 PMC2857316
- [20]Mells GF, Floyd JA, Morley KI, Cordell HJ, Franklin CS, et al (2011) Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat Genet 43: 329– 332. 21399635 PMC3071550
- [21]Hirschfield G, Invernizzi P (2011) Progress in the Genetics of Primary Biliary Cirrhosis. Seminars in Liver Disease 31: 147– 156. 21538281
- [23]Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, et al (2009) Primary biliary cirrhosis. Hepatology 50: 291– 308. 19554543
- [24]Corpechot C, Poupon R (2007) Geotherapeutics of primary biliary cirrhosis: Bright and sunny around the Mediterranean but still cloudy and foggy in the United Kingdom. Hepatology 46: 963– 965. 17894325
- [25]Metcalf JV, Mitchison HC, Palmer JM, Jones DE, Bassendine MF, et al (1996) Natural history of early primary biliary cirrhosis. Lancet 348: 1399– 1402. 8937278
- [26]Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, et al (2008) Serum microRNAs are promising novel biomarkers. PLoS One 3: e3148. 18773077 PMC2519789
- [27]Martin M (2011) Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet journal 17: 10– 12.
- [28]Robinson MD, Oshlack A (2010) A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biology 11: R25. 20196867 PMC2864565
- [29]Balaga O, Friedman Y, Linial M (2012) Toward a combinatorial nature of microRNA regulation in human cells. Nucleic Acids Res 40: 9404– 9416. 22904063 PMC3479204
- [30]Juran BD, Lazaridis KN (2010) Update on the genetics and genomics of PBC. J Autoimmun 35: 181– 187. 20638243 PMC2956841
- [31]Zhang R, Peng Y, Wang W, Su B (2007) Rapid evolution of an X-linked microRNA cluster in primates. Genome Res 17: 612– 617. 17416744 PMC1855169
- [32]Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, et al (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proceedings of the National Academy of Sciences 105: 10513– 10518. PMC2492472 18663219
- [33]Ai J, Zhang R, Li Y, Pu J, Lu Y, et al (2010) Circulating microRNA-1 as a potential novel biomarker for acute myocardial infarction. Biochemical and Biophysical Research Communications 391: 73– 77. 19896465
- [34]Chim SSC, Shing TKF, Hung ECW, Leung Ty, Lau Tk, et al (2008) Detection and Characterization of Placental MicroRNAs in Maternal Plasma. Clinical Chemistry 54: 482– 490. 18218722
- [35]Starkey Lewis PJ, Dear J, Platt V, Simpson KJ, Craig DGN, et al (2011) Circulating microRNAs as potential markers of human drug-induced liver injury. Hepatology 54: 1767– 1776. 22045675
- [37]Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, et al (2010) Circulating microRNAs in plasma of patients with gastric cancers. British Journal of Cancer 102: 1174– 1179. 20234369 PMC2853097
- [38]Kong X, Du Y, Wang G, Gao J, Gong Y, et al (2010) Detection of Differentially Expressed microRNAs in Serum of Pancreatic Ductal Adenocarcinoma Patients: miR-196a Could Be a Potential Marker for Poor Prognosis. Digestive Diseases and Sciences 56: 602– 609. 20614181
- [39]Silva J, Garcia V, Zaballos A, Provencio M, Lombardia L, et al (2010) Vesicle-related microRNAs in plasma of nonsmall cell lung cancer patients and correlation with survival. European Respiratory Journal 37: 617– 623. 20595154
- [40]Li M, Marin-Muller C, Bharadwaj U, Chow K-H, Yao Q, et al (2008) MicroRNAs: Control and Loss of Control in Human Physiology and Disease. World Journal of Surgery 33: 667– 684. PMC2933043 19030926
- [41]Berg CP, Stein GM, Keppeler H, Gregor M, Wesselborg S, et al (2007) Apoptosis-associated antigens recognized by autoantibodies in patients with the autoimmune liver disease primary biliary cirrhosis. Apoptosis 13: 63– 75. 18060504
- [42]Liang Y, Yang Z, Li C, Zhu Y, Zhang L, et al (2008) Characterisation of TNF-related apoptosis-inducing ligand in peripheral blood in patients with primary biliary cirrhosis. Clinical and Experimental Medicine 8: 1– 7. 18385934
- [43]Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, et al (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25: 25– 29. 10802651 PMC3037419
- [44]Nakagome Y, Ueno Y, Kogure T, Fukushima K, Moritoki Y, et al (2007) Autoimmune cholangitis in NOD.c3c4 mice is associated with cholangiocyte-specific Fas antigen deficiency. J Autoimmun 29: 20– 29. 17482429
- [45]Singh R, Bullard J, Kalra M, Assefa S, Kaul AK, et al (2011) Status of bacterial colonization, Toll-like receptor expression and nuclear factor-kappa B activation in normal and diseased human livers. Clinical Immunology 138: 41– 49. 20940109
- [46]Kyriakou DS, Alexandrakis MG, Zachou K, Passam F, Stathakis NE, et al (2003) Hemopoietic progenitor cells and bone marrow stromal cells in patients with autoimmune hepatitis type 1 and primary biliary cirrhosis. J Hepatol 39: 679– 685. 14568247
- [47]Maglott D, Ostell J, Pruitt KD, Tatusova T (2010) Entrez Gene: gene-centered information at NCBI. Nucleic Acids Research 39: D52– D57. 21115458 PMC3013746
- [48]Kozomara A, Griffiths-Jones S (2010) miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Research 39: D152– D157. 21037258 PMC3013655
- [49]Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society 57: 289– 300.
- [51]Friedman Y, Naamati G, Linial M (2010) MiRror: a combinatorial analysis web tool for ensembles of microRNAs and their targets. Bioinformatics 26: 1920– 1921. 20529892
- [52]Dennis G Jr, Sherman BT, Hosack DA, Yang J, Gao W, et al (2003) DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol 4: P3. 12734009
- [53]Knodell RG, Ishak KG, Black WC, Chen TS, Craig R, et al (1981) Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1: 431– 435. 7308988
- [54]Ludwig J, Dickson ER, McDonald GS (1978) Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis). Virchows Arch A Pathol Anat Histol 379: 103– 112. 150690
- [55]Scheuer P (1967) Primary biliary cirrhosis. Proceedings of the Royal Society of Medicine 60: 1257– 1260. 6066569 PMC1901478
- [56]Ward JH (1963) Hierarchical Grouping to Optimize an Objective Function. Journal of the American Statistical Association 58: 236– 244.
Cited by
Sorted by citations
The immunobiology of female predominance in primary biliary cholangitis
Gerussi, A., Cristoferi, L., Carbone, M., Asselta, R., & Invernizzi, P. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.10.015 · Cited by 41 · see citing works
Functional interaction between miR-505-3p and miR-21 contributes to GBM suppression
Banadkooki, M. Z., Soltani, B. M., & Mowla, S. J. (2026) · Scientific Reports · doi:10.1038/s41598-026-59926-5
- Authors
- Ninomiya, M., Kondo, Y., Funayama, R., Nagashima, T., Kogure, T., Kakazu, E., Kimura, O., Ueno, Y., Nakayama, K., & Shimosegawa, T.
- Affiliations
- Tohoku University Hospital (JP)
- Tohoku University (JP)
- Yamagata University (JP)
- Corresponding author
- Kondo, Yasuteru
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-06-12
- Volume
- 8
- Issue
- 6
- Pages
- e66086
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3680413
- OpenAlex
- W2041990656
- Cited by
- 83
- References
- 4
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 11 · 2017: 12 · 2016: 15 · 2015: 10 · 2014: 9 · 2013: 1
- FWCI
- 7.26
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Japan Society for the Promotion of Science (24700951, 23790765)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- primary biliary cirrhosis, microRNA expression profiles, serum microRNA, miR-197-3p, circulating biomarkers, viral hepatitis, differentially expressed miRNAs, miRNA target prediction
- MeSH terms
- Aged, Female, Humans, Liver Cirrhosis, Biliary, Male, Middle Aged, Biomarkers, Cluster Analysis, Reverse Transcriptase Polymerase Chain Reaction, Gene Expression Profiling, MicroRNAs, High-Throughput Nucleotide Sequencing
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.
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 ›
Are you an author, or do you see a problem with this page? Request a review