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Association of the microRNA-499 variants with susceptibility to hepatocellular carcinoma in a Chinese population

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Abstract

microRNAs (miRNAs) are a new class of small non-coding RNAs that function as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNA may contribute to cancer development. We hypothesized that genetic variations of the miRNA could be associated with the risk of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A total of 100 patients with HCC, 100 cases of chronic hepatitis B and 100 health adults were enrolled in this present study. Two common polymorphisms in pre-miRNAs: Homo sapiens miRNA-146a (hsa-mir-146a) (rs291016, guanine to cytosine [G-C]) and hsa-mir-499 (rs3746444; adenine to guanine [C-T]) were genotyped by PCR-Restriction Fragment Length Polymorphism and confirmed by bidirectional DNA sequencing. Significant differences were found in frequency and distribution of the genotypes of miRNA-499 between the HCC and the control group. Compared with miRNA-499 T/T, the odds ratio (OR) of patients with miRNA-499 C/C for developing HCC was 3.630 (95% CI: 1.545–8.532), and OR for developing HBV-related HCC was 3.133 (95% CI: 1.248–7.861). There was no significant association between miRNA-146a polymorphism and the risk of HCC in all subjects. Our results suggested that hsa-mir-499 polymorphism was associated with susceptibility to HBV-related HCC in Chinese population. Further characterization of miRNA SNPs may open new avenue for the study of cancer and therapeutic interventions.

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References

  1. Kao JH, Chen DS (2002) Global control of hepatitis B virus infection. Lancet Infect Dis 2:395–403

    Article  PubMed  Google Scholar 

  2. El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576

    Article  PubMed  CAS  Google Scholar 

  3. Thorgeirsson SS, Grisham JW (2002) Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 31:339–346

    Article  PubMed  CAS  Google Scholar 

  4. He L, Hannon GJ (2004) microRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531

    Article  PubMed  CAS  Google Scholar 

  5. Bartel DP (2004) microRNAs: genomics, biogenesis, mechanism and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  6. Wienholds E, Plasterk RH (2005) MicroRNA function in animal development. FEBS Lett 579:5911–5922

    Article  PubMed  CAS  Google Scholar 

  7. Chen JF, Mandel EM, Thomson JM, Wu Q, Callis TE, Hammond SM, Conlon FL, Wang DZ (2006) The role of microRNA-1 and microRNA-133 in skeletal muscle proliferation and differentiation. Nat Genet 38:228–233

    Article  PubMed  CAS  Google Scholar 

  8. Brennecke J, Hipfner DR, Stark A, Russell RB, Cohen SM (2003) bantam encodes a developmentally regulated microRNA that controls cell proliferation and regulates the proapoptotic gene hid in Drosophila. Cell 113:25–36

    Article  PubMed  CAS  Google Scholar 

  9. Cimmino A, Calin GA, Fabbri M, Iorio MV, Ferracin M, Shimizu M, Wojcik SE, Aqeilan RI, Zupo S, Dono M, Rassenti L, Alder H, Volinia S, Liu CG, Kipps TJ, Negrini M, Croce CM (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci USA 102:13944–13949

    Article  PubMed  CAS  Google Scholar 

  10. Skalsky RL, Cullen BR (2011) Reduced expression of brain-enriched microRNAs in glioblastomas permits targeted regulation of a cell death gene. PLoS One 6(9):e24248

    Google Scholar 

  11. Hatfield SD, Shcherbata HR, Fischer KA, Nakahara K, Carthew RW, Ruohola-Baker H (2005) Stem cell division is regulated by the microRNA pathway. Nature 435:974–978

    Article  PubMed  CAS  Google Scholar 

  12. Ambros V (2003) MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell 113:673–676

    Article  PubMed  CAS  Google Scholar 

  13. Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6:259–269

    Article  PubMed  CAS  Google Scholar 

  14. Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866

    Article  PubMed  CAS  Google Scholar 

  15. Bartel DP (2004) microRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  PubMed  CAS  Google Scholar 

  16. Loktionov A (2004) Common gene polymorphisms, cancer progression and prognosis. Cancer Lett 208:1–33

    Article  PubMed  CAS  Google Scholar 

  17. Srivatanakul P, Sriplung H, Deerasamee S (2004) Epidemiology of liver cancer: an overview. Asian Pac J Cancer Prev 5:118–125

    PubMed  Google Scholar 

  18. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838

    Article  PubMed  CAS  Google Scholar 

  19. Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A (2008) Common SNP in pre-miR-146a decreases mature miRNA expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci USA 105:7269–7274

    Article  PubMed  CAS  Google Scholar 

  20. Xu T, Zhu Y, Wei QK, Yuan Y, Zhou F, Ge YY, Yang JR, Su H, Zhuang SM (2008) A functional polymorphism in the miR-146a gene is associated with the risk for hepatocellular carcinoma. Carcinogenesis 29:2126–2131

    Article  PubMed  CAS  Google Scholar 

  21. Liu Z, Li G, Wei S, Niu J, El-Naggar AK, Sturgis EM, Wei Q (2010) Genetic variants in selected pre-microRNA genes and the risk of squamous cell carcinoma of the head and neck. Cancer 116:4753–4760

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported in part by the National Science Foundation of China (Grant No. 81071621 and 30973378), the Natural Science Foundation of Chongqing, China (Grant No. CSTC, 2010BB5390), the Science Foundation of Chongqing Municipal Bureau of Health (Grant No. 2010-2-090) and the Medical Science Foundation of the First Affiliated Hospital of Chongqing Medical University (Grant No. YXJJ 2009-12).

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Authors and Affiliations

  1. Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China

    Yu Xiang, Song Fan, Ju Cao, Shifeng Huang & Li-ping Zhang

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  1. Yu Xiang
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  2. Song Fan
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  3. Ju Cao
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  4. Shifeng Huang
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  5. Li-ping Zhang
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Correspondence to Li-ping Zhang.

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Yu Xiang and Song Fan contributed equally to this work.

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Xiang, Y., Fan, S., Cao, J. et al. Association of the microRNA-499 variants with susceptibility to hepatocellular carcinoma in a Chinese population. Mol Biol Rep 39, 7019–7023 (2012). https://doi.org/10.1007/s11033-012-1532-0

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  • DOI: https://doi.org/10.1007/s11033-012-1532-0

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