Population differences in microRNA expression and biological implications
Open accessAbstract
Population differences observed for complex traits may be attributed to the combined effect of socioeconomic, environmental, genetic and epigenetic factors. To better understand population differences in complex traits, genome-wide genetic and gene expression differences among ethnic populations have been studied. Here we set out to evaluate population differences in small non-coding RNAs through an evaluation of microRNA (miRNA) baseline expression in HapMap lymphoblastoid cell lines (LCLs) derived from 53 CEU (Utah residents with northern and western European ancestry) and 54 YRI (African from Ibadan, Nigeria). Using the Exiqon miRCURYTM LNA arrays, we found that 16% of all miRNAs evaluated in our study differ significantly between these 2 ethnic groups (pBonferroni corrected< 0.05). Furthermore, we explored the potential biological function of these observed differentially expressed miRNAs by comprehensively examining their effect on the transcriptome and their relationship with cellular sensitivity drug phenotypes. After multiple testing adjustment (false discovery rate (FDR)< 0.1), we found that 55% and 88% of the differentially expressed miRNAs were significantly and inversely correlated with an mRNA expression phenotype in the CEU and YRI samples, respectively. Interestingly, a substantial proportion (64%) of these miRNAs correlated with cellular sensitivity to chemotherapeutic agents (FDR< 0.05). Lastly, upon performing a genome-wide association study between SNPs and miRNA expression, we identified a large number of SNPs exhibiting different allele frequencies that affect the expression of these differentially expressed miRNAs, suggesting the role of genetic variants in mediating the observed population differences.
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?
Population-specific genetic and environmental factors may influence miR-21 expression, leading to variations in diagnostic performance and prognostic utility.
“Addressing this gap is crucial, as population-specific genetic and environmental factors may influence microRNA e.g.miR-21 expression, leading to variations in the diagnostic performance and prognostic utility as well as therapeutic response [14,15].”
From miR-21 as a diagnostic and prognostic biomarker in glioma: tissue and serum expression analysis in a Pakistani cohort (2026) · cites this paper as [14]
The Discussion reports population differences in miRNA expression in CEU and YRI cell lines, and the Introduction suggests genetic variants may help explain them. The paper also links some of those miRNAs to in-vitro chemotherapy sensitivity. It does not establish population-specific genetic or environmental effects on miR-21, or show resulting differences in diagnostic performance or prognostic utility; the miR-21 prognosis item appears only in the References. Page numbers are unavailable in our copy. (LLM, conf=0.87)
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
The International HapMap Project
†The International HapMap Consortium, Genotyping centres: Baylor College of Medicine and ParAllele BioScience, Gibbs, R. A., Belmont, J. W., Hardenbol, P., Willis, T. D., Yu, F., Chinese HapMap Consortium, Yang, H., Ch'ang, L.-Y., et al. (2003) · Nature · doi:10.1038/nature02168 · Cited by 6,057 · see citing works
Self-citationXie, X., Lu, J., Kulbokas, E. J., Golub, T. R., Mootha, V., Lindblad-Toh, K., Lander, E. S., & Kellis, M. (2005) · Nature · doi:10.1038/nature03441 · Cited by 1,872 · see citing works
Flagged first, then by citations
Research works printed but not linked: 56
- Johnson JA. Predictability of the effects of race or ethnicity on pharmacokinetics of drugs. Int J Clin Pharmacol Ther 2000; 38:53-60; PMID: 10706191.
- O'Donnell PH, Dolan ME. Cancer Pharmacoethnicity: Ethnic Differences in Susceptibility to the Effects of Chemotherapy. Clin Cancer Res 2009; 15:4806-14; PMID: 19622575; DOI: 10.1158/1078-0432.CCR- 09-0344. · DOI
- Fitzgerald KT. Ethics at the intersection of pharma- coethnicity. Clin Pharmacol Ther 2008; 84:424-6; PMID: 18596680; DOI: 10.1038/clpt.2008.126. · DOI
- Lin CP, Liu J, Chow J, Liu C, Liu H. Small- molecule c-Myc inhibitor, 10058-F4, inhibits pro- liferation, downregulates human telomerase reverse transcriptase and enhances chemosensitivity in human hepatocellular carcinoma cells. Anticancer Drugs 2007; 18:161-70; PMID: 17159602; DOI: 10.1097/ CAD.0b013e3280109424. · DOI
- Armengol L, Villatoro S, González J, Pantano L, García-Aragonés M, Rabionet R, et al. Identification of copy number variants defining genomic differ- ences among major human groups. PLoS ONE 2009; 4:7230; PMID: 19789632; DOI: 10.1371/journal. pone.0007230. · DOI
- Zhang W, Duan S, Kistner EO, Bleibel WK, Huang RS, Clark TA, et al. Evaluation of Genetic Variation Contributing to Differences in Gene Expression between Populations. Am J Hum Genet 2008; 82:631-40; PMID: 18313023; DOI: 10.1016/j. ajhg.2007.12.015. · DOI
- Spielman RS, Bastone LA, Burdick JT, Morley M, Ewens WJ, Cheung VG. Common genetic variants account for differences in gene expression among ethnic groups. Nat Genet 2007; 39:226-31; PMID: 17206142; DOI: 10.1038/ng1955. · DOI
- Storey JD, Madeoy J, Strout J, Murfel M, Ronald J, Akey J. Gene-expression variation within and among human populations. Am J Hum Genet 2007; 80:502- 9; PMID: 17273971; DOI: 10.1086/512017. · DOI
- Chang TC, Mendell J. MicroRNAs in vertebrate physiology and human disease. Annu Rev Genomics Hum Genet 2007; 8:215-39; PMID: 17506656; DOI: 10.1146/annurev.genom.8.080706.092351. · DOI
- Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk R, Cuppen E. Phylogenetic shadowing and computational identification of human microRNA genes. Cell 2005; 120:21-4; PMID: 15652478; DOI: 10.1016/j.cell.2004.12.031. · DOI · Paper page
- Lewis BP, Burge C, Bartel D. Conserved seed pairing, often flanked by adenosines, indicates that thou- sands of human genes are microRNA targets. Cell 2005; 120:15-20; PMID: 15652477; DOI: 10.1016/j. cell.2004.12.035. · DOI · Paper page
- van Rooij E, Olson E. MicroRNAs: powerful new regulators of heart disease and provocative therapeutic targets. J Clin Invest 2007; 117:2369-76; PMID: 17786230; DOI: 10.1172/JCI33099. · DOI
- Calin GA, Dumitru C, Shimizu M, Bichi R, Zupo S, Noch E, et al. Frequent deletions and downregulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 2002; 99:15524-9; PMID: 12434020; DOI: 10.1073/ pnas.242606799. · DOI · Paper page
- Calin GA, Liu C, Sevignani C, Ferracin M, Felli N, Dumitru C, et al. MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA 2004; 101:11755-60; PMID: 15284443; DOI: 10.1073/pnas.0404432101. · DOI
- Calin GA, Sevignani C, Dumitru C, Hyslop T, Noch E, Yendamuri S, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci USA 2004; 101:2999-3004; PMID: 14973191; DOI: 10.1073/ pnas.0307323101. · DOI
- Lu Y, Ryan S, Eilliot D, Bignell G, Futreal P, Ellison D, et al. Amplification and overexpression of Hsa-miR- 30b, Hsa-miR-30d and KHDRBS3 at 8q24.22-q24.23 in medulloblastoma. PLoS One 2009; 4:6159; PMID: 19584924; DOI: 10.1371/journal.pone.0006159. · DOI
- Araki T, Milbrandt J. ZNRF Proteins Constitute a Family of Presynaptic E3 Ubiquitin Ligases. J Neurosci 2003; 23:9385-94; PMID: 14561866.
- Yoshida K, Watanabe M, Hatakeyama S. ZNRF1 interacts with tubulin and regulates cell morphogenesis. Biochem Biophys Res Commun 2009; 389:506-11; PMID: 19737534; DOI: 10.1016/j.bbrc.2009.09.011. · DOI
- Dausset J, Cann H, Cohen D, Lathrop M, Lalouel J, White R. Centre d'etude du polymorphisme humain (CEPH): collaborative genetic mapping of the human genome. Genomics 1990; 6:575-7; PMID: 2184120; DOI: 10.1016/0888-7543(90)90491-C. · DOI
- Akey JM, Biswas S, Leek JT, Storey JD. On the design and analysis of gene expression studies in human popu- lations. Nat Genet 2007; 39:807-8; PMID: 17597765; DOI: 10.1038/ng0707-807. · DOI
- Ritchie ME, Silver J, Oshlack A, Holmes M, Diyagama D, Holloway A, et al. A comparison of background correction methods for two-colour microarrays. Bioinformatics 2007; 23:2700-7; PMID: 17720982; DOI: 10.1093/bioinformatics/btm412. · DOI · Paper page
- Gamazon ER, Im HK, Duan S, Lussier YA, Cox NJ, Dolan ME. ExprTarget: An integrative approach to predicting human microRNA targets. PLoS One 2010; 5:13534; PMID: 20975837; DOI: 10.1371/journal. pone.0013534. · DOI
- Storey JD, Tibshirani R. Statistical significance for genome-wide studies. Proc Natl Acad Sci USA 2003; 100:9440-5; PMID: 12883005; DOI: 10.1073/ pnas.1530509100. · DOI · Paper page
- Huang RS, Duan S, Shukla SJ, Kistner EO, Clark TA, Chen TX, et al. Identification of Genetic Variants Contributing to Cisplatin-Induced Cytotoxicity using a Genome-wide Approach. Am J Hum Genet 2007; 81:427-37; PMID: 17701890; DOI: 10.1086/519850. · DOI
- Duan S, Zhang W, Bleibel W, Cox N, Dolan ME. SNPinProbe_1.0: A database for filtering out probes in the Affymetrix GeneChip ® Human Exon 1.0 ST array potentially affected by SNPs. Bioinformation 2008; 2:469-70; PMID: 18841244.
- Griffiths-Jones S, Saini H. Dongen Sv, Enright A. miR- Base: tools for microRNA genomics. Nucleic Acids Res 2008; 36:154-8; PMID: 17991681; DOI: 10.1093/ nar/gkm952. · DOI
- Holsinger KE, Weir B. Genetics in geographically structured populations: defining, estimating and inter- preting F(ST). Nat Rev Genet 2009; 10:639-50; PMID: 19687804; DOI: 10.1038/nrg2611. · DOI
- Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2-delta delta CT method. Methods 2001; 25:402- 8; PMID: 11846609; DOI: 10.1006/meth.2001.1262. · DOI · Paper page
- Taylor AL, Ziesche S, Yancy C, Carson P, D'Agostino RJ, Ferdinand K, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med 2004; 351:2049-57; PMID: 15533851; DOI: 10.1056/NEJMoa042934. · DOI · Paper page
- Moses KA, Paciorek AT, Penson DF, Carroll PR, Master VA. Impact of Ethnicity on Primary Treatment Choice and Mortality in Men With Prostate Cancer: Data From CaPSURE. J Clin Oncol 2010; 28:1069-74; PMID: 20100957; DOI: 10.1200/JCO.2009.26.2469. · DOI
- Zhang R, Su B. MicroRNA regulation and the vari- ability of human cortical gene expression. Nucleic Acids Res 2008; 36:4621-8; PMID: 18617573; DOI: 10.1093/nar/gkn431. · DOI
- Theodore S, Rhim J, Turner T, Yates C. MiRNA 26a expression in a novel panel of African American pros- tate cancer cell lines. Ethn Dis 2010; 20:96-100.
- Zhang HZ, Wei Y, Wang M, Wu C, Yang Y, Chen J, et al. Association of CD133 and endothelin-converting enzyme expressions with prognosis of non-small cell lung carcinoma. Nan Fang Yi Ke Da Xue Xue Bao 2007; 27:696-9; PMID: 17545092.
- Khamaisi M, Dahan R, Hamed S, Abassi Z, Heyman S, Raz I. Role of protein kinase C in the expression of endothelin converting enzyme-1. Endocrinology 2009; 150:1440-9; PMID: 18974277; DOI: 10.1210/ en.2008-0524. · DOI
- Wang S, Wang R, Chen L, Bennett D, Dickson D, Wang D. Expression and functional profiling of neprilysin, insulin-degrading enzyme and endo- thelin-converting enzyme in prospectively studied elderly and Alzheimer's brain. J Neurochem 2010; 115:47-57; PMID: 20663017; DOI: 10.1111/j.1471- 4159.2010.06899.x. · DOI
- Montag J, Hitt R, Opitz L, Schulz-Schaeffer W, Hunsmann G, Motzkus D. Upregulation of miRNA hsa-miR-342-3p in experimental and idiopathic prion disease. Mol Neurodegener 2009; 4:36; PMID: 19712440; DOI: 10.1186/1750-1326-4-36. · DOI
- Saba R, Goodman CD, Huzarewich RL, Robertson C, Booth SA. A miRNA signature of prion induced neurodegeneration. PLoS One 2008; 3:3652; PMID: 18987751; DOI: 10.1371/journal.pone.0003652. · DOI · Paper page
- Hsu YC, Yuan S, Chen HY, Yu SL, Liu CH, Hsu PY, et al. A Four-Gene Signature from NCI-60 Cell Line for Survival Prediction in Nonâ€"Small Cell Lung Cancer. Clin Cancer Res 2009; 15:7309-15; PMID: 19920108; DOI: 10.1158/1078-0432.CCR-09-1572. · DOI
- Gao W, Shen H, Liu L, Xu J, Xu J, Shu Y. MiR-21 overexpression in human primary squamous cell lung carcinoma is associated with poor patient prognosis. J Cancer Res Clin Oncol 2011; 137:557-66; PMID: 20508945.
- Yang RF, Chen L, Li J, Li C, Xu J, Wu Y, et al. microRNA-21 and microRNA-30b expression in mul- tiple myeloma. Zhonghua Xue Ye Xue Za Zhi 2010; 31:38-41; PMID: 20302778.
- Wszolek MF, Rieger-Christ K, Kenney P, Gould J, Silva Neto B, Lavoie A, et al. A MicroRNA expression profile defining the invasive bladder tumor phenotype. Urol Oncol 2009; Epub ahead of print; PMID: 19945312; DOI: 10.1016/j.urolonc.2009.08.024. · DOI
- Bruchova H, Merkerova M, Prchal J. Aberrant expres- sion of microRNA in polycythemia vera. haematologica 2008; 93:1009-16.
- Takagi S, Nakajima M, Mohri T, Yokoi T. Post- transcriptional regulation of human pregnane X recep- tor by microRNA affects the expression of cytochrome P450 3A4. J Biol Chem 2008; 283:9674-80; PMID: 18268015; DOI: 10.1074/jbc.M709382200. · DOI
- Tsuchiya Y, Nakajima M, Takagi S, Taniya T, Yokoi T. MicroRNA regulates the expression of human cytochrome P450 1B1. Cancer Res 2006; 66:9090-8; PMID: 16982751; DOI: 10.1158/0008-5472.CAN- 06-1403. · DOI
- Boren T, Cui S, Chan G, Dressman H, Lancaster J. MicroRNAs that underlie response to salvage che- motherapy in ovarian cancer. J Clin Oncol 2007; 25:10542.
- Weidhaas JB, Babar I, Nallur S, Trang P, Roush S, Boehm M, et al. MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy. Cancer Res 2007; 67:11111-6; PMID: 18056433; DOI: 10.1158/0008-5472.CAN-07-2858. · DOI
- Yang H, Kong W, He L, Zhao J, O'Donnell J, Wang J, et al. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cis- platin resistance by targeting PTEN. Cancer Res 2008; 68:425-33; PMID: 18199536; DOI: 10.1158/0008- 5472.CAN-07-2488. · DOI
- Mishra PJ, Humeniuk R, Mishra P, Longo-Sorbello G, Banerjee D, Bertino J. A miR-24 microRNA binding- site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance. Proc Natl Acad Sci USA 2007; 104:13513-8; PMID: 17686970; DOI: 10.1073/pnas.0706217104. · DOI
- Zhang W, Dolan ME. Beyond the HapMap Genotypic Data: Prospects of Deep Resequencing Projects. Curr Bioinform 2008; 3:178; PMID: 20151045; DOI: 10.2174/157489308785909232. · DOI
- Zhang W, Dolan ME. Use of cell lines in the inves- tigation of pharmacogenetic loci. Curr Pharm Des 2009; 15:3782-95; PMID: 19925429; DOI: 10.2174/138161209789649475. · DOI
- Huang RS, Kistner EO, Bleibel WK, Shukla SJ, Dolan ME. Effect of population and gender on chemothera- peutic agent-induced cytotoxicity. Mol Cancer Ther 2007; 6:31-6; PMID: 17237264; DOI: 10.1158/1535- 7163.MCT-06-0591. · DOI
- Hartford CM, Duan S, Delaney S, Mi S, Kistner E, Lamba J, et al. Population-specific genetic variants important in susceptibility to cytarabine arabino- side cytotoxicity. Blood 2009; 113:2145-53; PMID: 19109566; DOI: 10.1182/blood-2008-05-154302. · DOI
- Duan S, Mi S, Zhang W, Dolan ME. Comprehensive analysis of the impact of SNPs and CNVs on human microRNAs and their regulatory genes. RNA Biol 2009; 6:412-25; PMID: 19458495; DOI: 10.4161/ rna.6.4.8830. · DOI
- Iafrate AJ, Feuk L, Rivera M, Listewnik M, Donahoe P, Qi Y, et al. Detection of large-scale variation in the human genome. Nat Genet 2004; 36:949-51; PMID: 15286789; DOI: 10.1038/ng1416. · DOI · Paper page
- Evans S, Metcalfe C, Ibrahim F, Persad R, Ben-Shlomo Y. Investigating Black-White differences in prostate cancer prognosis: A systematic review and meta-analy- sis. Int J Cancer 2008; 123:430-5; PMID: 18452170; DOI: 10.1002/ijc.23500. · DOI
- Laiyemo AO, Doubeni C, Pinsky PF, Doria-Rose VP, Bresalier R, Lamerato LE, et al. Race and Colorectal Cancer Disparities: Health-Care Utilization vs. Different Cancer Susceptibilities. J Natl Cancer Inst 2010; 102:538-46; PMID: 20357245; DOI: 10.1093/ jnci/djq068. · DOI
Cited by
Sorted by citations
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche
Study, A. O. C., Perry, J. R. B., The GENICA Network, kConFab, Study, T. L. C., The InterAct Consortium, Early Growth Genetics (EGG) Consortium, Day, F., Elks, C. E., Sulem, P., et al. (2014) · Nature · doi:10.1038/nature13545 · Cited by 604 · see citing works
Circulating microRNA profile throughout the menstrual cycle
Rekker, K., Saare, M., Roost, A. M., Salumets, A., & Peters, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0081166 · Cited by 52 · see citing works
Laghari, A. A., Sufiyan, S., Amin, W., Ilyas, S., Naeem, S., Adnan, U., Abidi, S. H., Uddin, S., Enam, S. A., & Mughal, N. (2026) · Journal of Neuro-Oncology · doi:10.1007/s11060-025-05287-4 · Cited by 1 · see citing works
“Addressing this gap is crucial, as population-specific genetic and environmental factors may influence microRNA e.g. miR-21 expression, leading to variations in the diagnostic performance and prognostic utility as well as therapeutic response [14, 15].”
- Authors
- Huang, R. S., Gamazon, E. R., Ziliak, D., Wen, Y., Im, H. K., Zhang, W., Wing, C., Duan, S., Bleibel, W. K., Cox, N. J., & Dolan, M. E.
- Affiliations
- University of Illinois Chicago (US)
- University of Chicago (US)
- Corresponding author
- Huang, R. Stephanie
- ORCID
- Venue
- RNA Biology
- Publisher
- Informa UK Limited
- Published
- 2011-07
- Volume
- 8
- Issue
- 4
- Pages
- 692-701
- ISSN
- 1547-6286 (ISSN-L)
- 1555-8584
- PMC
- PMC3225983
- OpenAlex
- W2036607475
- Cited by
- 171
- References
- 2
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 8 · 2023: 6 · 2022: 17 · 2021: 13 · 2020: 13 · 2019: 16 · 2018: 12 · 2017: 11 · 2016: 19 · 2015: 5 · 2014: 15 · 2013: 12 · 2012: 9
- FWCI
- 3.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- RNA Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (CA 14599, CA139278, P30‐CA14599, R21CA139278, P50CA125183, CA125183, P30CA014599)
- National Institute of General Medical Sciences (K08GM089941, U01 GM61393, U01GM061393)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Keywords
- microRNA expression, population differences, ethnic differences, CEU, lymphoblastoid cell lines, small RNA, miRNA-mRNA correlation, transcriptome, drug sensitivity, chemosensitivity, single nucleotide polymorphisms, genetic variants, allele frequency, HapMap
- MeSH terms
- Cell Line, Gene Frequency, Humans, Genetic Variation, Polymorphism, Single Nucleotide, Gene Expression Profiling, MicroRNAs, Black People, White People, Genome-Wide Association Study, Transcriptome, HapMap Project
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