Molecular Biology Reports

, Volume 39, Issue 6, pp 7019–7023

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

  • Yu Xiang
  • Song Fan
  • Ju Cao
  • Shifeng Huang
  • Li-ping Zhang
Article

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.

Keywords

Hepatitis B virus Hepatocellular carcinoma Single nucleotide polymorphisms microRNAs miRNA-146a miRNA-499 

References

  1. 1.
    Kao JH, Chen DS (2002) Global control of hepatitis B virus infection. Lancet Infect Dis 2:395–403PubMedCrossRefGoogle Scholar
  2. 2.
    El-Serag HB, Rudolph KL (2007) Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology 132:2557–2576PubMedCrossRefGoogle Scholar
  3. 3.
    Thorgeirsson SS, Grisham JW (2002) Molecular pathogenesis of human hepatocellular carcinoma. Nat Genet 31:339–346PubMedCrossRefGoogle Scholar
  4. 4.
    He L, Hannon GJ (2004) microRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531PubMedCrossRefGoogle Scholar
  5. 5.
    Bartel DP (2004) microRNAs: genomics, biogenesis, mechanism and function. Cell 116:281–297PubMedCrossRefGoogle Scholar
  6. 6.
    Wienholds E, Plasterk RH (2005) MicroRNA function in animal development. FEBS Lett 579:5911–5922PubMedCrossRefGoogle Scholar
  7. 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 38:228–233PubMedCrossRefGoogle Scholar
  8. 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 113:25–36PubMedCrossRefGoogle Scholar
  9. 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 102:13944–13949PubMedCrossRefGoogle Scholar
  10. 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):e24248Google Scholar
  11. 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 435:974–978PubMedCrossRefGoogle Scholar
  12. 12.
    Ambros V (2003) MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell 113:673–676PubMedCrossRefGoogle Scholar
  13. 13.
    Esquela-Kerscher A, Slack FJ (2006) Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer 6:259–269PubMedCrossRefGoogle Scholar
  14. 14.
    Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866PubMedCrossRefGoogle Scholar
  15. 15.
    Bartel DP (2004) microRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297PubMedCrossRefGoogle Scholar
  16. 16.
    Loktionov A (2004) Common gene polymorphisms, cancer progression and prognosis. Cancer Lett 208:1–33PubMedCrossRefGoogle Scholar
  17. 17.
    Srivatanakul P, Sriplung H, Deerasamee S (2004) Epidemiology of liver cancer: an overview. Asian Pac J Cancer Prev 5:118–125PubMedGoogle Scholar
  18. 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 435:834–838PubMedCrossRefGoogle Scholar
  19. 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 105:7269–7274PubMedCrossRefGoogle Scholar
  20. 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 29:2126–2131PubMedCrossRefGoogle Scholar
  21. 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 116:4753–4760PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Yu Xiang
    • 1
  • Song Fan
    • 1
  • Ju Cao
    • 1
  • Shifeng Huang
    • 1
  • Li-ping Zhang
    • 1
  1. 1.Department of Laboratory MedicineThe First Affiliated Hospital of Chongqing Medical UniversityChongqingPeople’s Republic of China

Personalised recommendations