Tumor Biology

, Volume 37, Issue 3, pp 4169–4174 | Cite as

MicroRNA-101 polymorphisms and risk of head and neck squamous cell carcinoma in a Chinese population

  • Limin Miao
  • Lihua Wang
  • Hua Yuan
  • Dong Hang
  • Longbiao Zhu
  • Jiangbo Du
  • Xun Zhu
  • Bing Li
  • Ruixia Wang
  • Hongxia Ma
  • Ning Chen
Original Article


MicroRNAs (miRNAs) play important roles in regulation of gene expressions and likely have involvement in cancer susceptibility and disease progression. MicroRNA-101 (miR-101) has been well established as a tumor suppressor, and aberrant expression of miR-101 levels has been previously reported in different malignancies including head and neck squamous cell carcinoma (HNSCC). However, the role of single nucleotide polymorphisms (SNPs) of miR-101 in the susceptibility to HNSCC remains unclear. In this study, we genotyped 11 selected SNPs of the miR-101 genes (including miR-101-1 and miR-101-2) in a case–control study including 576 HNSCC cases and 1552 cancer-free controls. For the main effect analysis, none of the 11 selected SNPs was associated with HNSCC risk. However, in the stratification analysis by tumor sites, rs578481 and rs705509 in pri-miR-101-1 were significantly associated with risk of oral squamous cell carcinoma (OSCC) (rs578481: adjusted odds ratio (OR) = 1.19, 95 % confidence interval (CI) 1.01–1.39, P = 0.036; rs705509: adjusted OR = 0.85, 95 % CI 0.73–0.98, P = 0.030). Furthermore, combined analysis of the two SNPs revealed that subjects carrying the risk alleles of rs578481 and rs705509 had increased risk of OSCC in a dose–response manner (P trend = 0.022). Compared with subjects carrying “0–2” risk alleles, subjects carrying “3–4” risk alleles presented a 1.38-fold increased risk of OSCC. In conclusion, our findings suggested that the SNPs rs578481 and rs705509 locating in pri-miR-101-1 may play a role in genetic susceptibility to OSCC, which may improve our understanding of the potential contribution of miRNA SNPs to cancer pathogenesis.


Head and neck squamous cell carcinoma MicroRNA Polymorphism Susceptibility Association 



Head and neck cancer


Head and neck squamous cell carcinoma


Oral squamous cell carcinoma


Untranslated region


Single nucleotide polymorphisms


Odds ratio


Confidence interval


Esophageal squamous cell carcinoma



This work was supported in part by the National Natural Science Foundation of China (81473048 and 81302361), Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine), Specialized Research Fund for the Doctoral Program of Higher Education of China (20133234120013), China Postdoctoral Science Foundation (2013 M540457), and Jiangsu Planned Projects for Postdoctoral Research Funds (1301018A).

Compliance with ethical standards

Conflicts of interest



  1. 1.
    Marcu LG, Yeoh E. A review of risk factors and genetic alterations in head and neck carcinogenesis and implications for current and future approaches to treatment. J Cancer Res Clin Oncol. 2009;135:1303–14.CrossRefPubMedGoogle Scholar
  2. 2.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.CrossRefPubMedGoogle Scholar
  3. 3.
    Sankaranarayanan R, Masuyer E, Swaminathan R, Ferlay J, Whelan S. Head and neck cancer: a global perspective on epidemiology and prognosis. Anticancer Res. 1998;18:4779–86.PubMedGoogle Scholar
  4. 4.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMedGoogle Scholar
  5. 5.
    Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–5.CrossRefPubMedGoogle Scholar
  6. 6.
    Semaan A, Qazi AM, Seward S, et al. MicroRNA-101 inhibits growth of epithelial ovarian cancer by relieving chromatin-mediated transcriptional repression of p21(waf(1)/cip(1)). Pharm Res. 2011;28:3079–90.CrossRefPubMedGoogle Scholar
  7. 7.
    Hu Z, Lin Y, Chen H, et al. MicroRNA-101 suppresses motility of bladder cancer cells by targeting c-Met. Biochem Biophys Res Commun. 2013;435:82–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Zhang Y, Guo X, Xiong L, et al. MicroRNA-101 suppresses SOX9-dependent tumorigenicity and promotes favorable prognosis of human hepatocellular carcinoma. FEBS Lett. 2012;586:4362–70.CrossRefPubMedGoogle Scholar
  9. 9.
    Lei Y, Li B, Tong S, et al. miR-101 suppresses vascular endothelial growth factor C that inhibits migration and invasion and enhances cisplatin chemosensitivity of bladder cancer cells. PLoS One. 2015;10:e0117809.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6:857–66.CrossRefPubMedGoogle Scholar
  11. 11.
    Calin GA, Sevignani C, Dumitru CD, et al. Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004;101:2999–3004.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Lu J, Getz G, Miska EA, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.CrossRefPubMedGoogle Scholar
  13. 13.
    Wu C, Li M, Hu C, Duan H. Prognostic role of microRNA polymorphisms in patients with advanced esophageal squamous cell carcinoma receiving platinum-based chemotherapy. Cancer Chemother Pharmacol. 2014;73:335–41.CrossRefPubMedGoogle Scholar
  14. 14.
    Xiong XD, Cho M, Cai XP, et al. A common variant in pre-miR-146 is associated with coronary artery disease risk and its mature miRNA expression. Mutat Res Fundam Mol Mech Mutagen. 2014;761:15–20.CrossRefGoogle Scholar
  15. 15.
    Jazdzewski K, Murray EL, Franssila K, Jarzab B, Schoenberg DR, de la Chapelle A. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc Natl Acad Sci U S A. 2008;105:7269–74.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Orsos Z, Szanyi I, Csejtei A, Gerlinger I, Ember I, Kiss I. Association of pre-miR-146a rs2910164 polymorphism with the risk of head and neck cancer. Anticancer Res. 2013;33:341–6.PubMedGoogle Scholar
  17. 17.
    Banerjee R, Mani RS, Russo N, et al. The tumor suppressor gene rap1GAP is silenced by miR-101-mediated EZH2 overexpression in invasive squamous cell carcinoma. Oncogene. 2011;30:4339–49.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Su H, Yang JR, Xu T, et al. MicroRNA-101, down-regulated in hepatocellular carcinoma, promotes apoptosis and suppresses tumorigenicity. Cancer Res. 2009;69:1135–42.CrossRefPubMedGoogle Scholar
  19. 19.
    Li S, Fu H, Wang Y, et al. MicroRNA-101 regulates expression of the v-fos FBJ murine osteosarcoma viral oncogene homolog (FOS) oncogene in human hepatocellular carcinoma. Hepatology (Baltimore, Md). 2009;49:1194–202.CrossRefGoogle Scholar
  20. 20.
    Buechner J, Tomte E, Haug BH, et al. Tumour-suppressor microRNAs let-7 and mir-101 target the proto-oncogene MYCN and inhibit cell proliferation in MYCN-amplified neuroblastoma. Br J Cancer. 2011;105:296–303.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lin C, Huang F, Li QZ, Zhang YJ. miR-101 suppresses tumor proliferation and migration, and induces apoptosis by targeting EZH2 in esophageal cancer cells. Int J Clin Exp Pathol. 2014;7:6543–50.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Bae JS, Kim JH, Pasaje CF, et al. Association study of genetic variations in microRNAs with the risk of hepatitis B-related liver diseases. Digestive and liver disease. Off J Ital Soc Gastroenterol Ital Assoc Study Liver. 2012;44:849–54.Google Scholar
  23. 23.
    Chen J, Qin Z, Jiang Y, et al. Genetic variations in the flanking regions of miR-101-2 are associated with increased risk of breast cancer. PLoS One. 2014;9:e86319.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    da Silva SD, Ferlito A, Takes RP, et al. Advances and applications of oral cancer basic research. Oral Oncol. 2011;47:783–91.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Limin Miao
    • 1
  • Lihua Wang
    • 2
  • Hua Yuan
    • 1
  • Dong Hang
    • 2
  • Longbiao Zhu
    • 1
  • Jiangbo Du
    • 2
  • Xun Zhu
    • 2
  • Bing Li
    • 1
  • Ruixia Wang
    • 1
  • Hongxia Ma
    • 2
    • 3
  • Ning Chen
    • 1
    • 4
  1. 1.Jiangsu Key Laboratory of Oral DiseasesNanjing Medical UniversityNanjingChina
  2. 2.Department of Epidemiology and Biostatistics, School of Public HealthNanjing Medical UniversityNanjingChina
  3. 3.Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingChina
  4. 4.Institute of StomatologyNanjing Medical UniversityNanjingChina

Personalised recommendations