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Tumor Biology

, Volume 35, Issue 12, pp 12127–12130 | Cite as

miR149 rs71428439 polymorphism and risk of clear cell renal cell carcinoma: a case–control study

  • Zhigang Wang
  • Meng Wei
  • Yi Ren
  • Hua Liu
  • Meng Wang
  • Kehui Shi
  • Hongli Jiang
Research Article

Abstract

Clear cell renal cell carcinoma (CCRCC) is the most common subtype of renal cell cancer and accounts for 70 % of renal cell cancer. CCRCC remains an enigmatic tumor type, as the molecular genetic mechanisms are still unclear. MicroRNA (miR) 149 functions as a tumor suppressor and plays an important role in the carcinogenesis of renal cells. In this study, we enrolled 1,000 CCRCC patients and 1,000 cancer-free controls to evaluate the association of miR149 rs71428439 with the risk of CCRCC by a case–control study to determine the effects on CCRCC risk. miR149 rs71428439 was significantly associated with increased CCRCC risk (odds ratio (OR) for trend = 1.53, P for trend = 4.04 × 10−11), with ORs (95 % confidence intervals (CIs)) of 1.42 (1.17–1.72) associated with AG genotype and 2.27 (1.76–2.94) associated with GG genotype, compared with subjects with AA genotype. The expression levels of miR149 in cancer tissues were significantly lower than those in adjacent normal tissues (P = 0.005), and per G allele has significantly lower miR149 levels in both tumor tissues and adjacent normal tissues. Our data suggest that the GG genotypes of miR149 rs71428439 predispose their carriers to CCRCC, and miR149 rs71428439 may be a new biomarker for predicting the risk of CCRCC.

Keywords

Polymorphism Renal cell carcinoma MicroRNA CCRCC miR149 

Notes

Acknowledgments

We thank all staff who were involved in the subject recruitment, telephone interviews, sample preparation, and laboratory assays for their hard works.

Conflicts of interest

None

References

  1. 1.
    Kidney cancer: CXCR4—a prognostic factor for renal cell carcinoma? Nature reviews urology 2014;11:247.Google Scholar
  2. 2.
    Loron MC, Grange S, Guerrot D, Di Fiore F, Freguin C, Hanoy M, Le Roy F, Poussard G, Etienne I, Legallicier B, Pfister C, Godin M, Bertrand D: Pneumocystis jirovecii pneumonia in everolimus-treated renal cell carcinoma. J Clin Oncol 2014Google Scholar
  3. 3.
    De Meerleer G, Khoo V, Escudier B, Joniau S, Bossi A, Ost P, et al. Radiotherapy for renal cell carcinoma. Lancet Oncol. 2014;15:e170–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Lornoy W, Becaus S, de Vleeschouwer M, Morelle V, Fonteyne E, Thienpoint L, et al. Renal cell carcinoma, a new complication of analgesic nephropathy. Lancet. 1986;1:1271–2.PubMedCrossRefGoogle Scholar
  5. 5.
    Renal cell carcinoma. Lancet 1976;2:887–888.Google Scholar
  6. 6.
    Brugarolas J: Molecular genetics of clear-cell renal cell carcinoma. J Clin Oncol 2014Google Scholar
  7. 7.
    Vergho D, Kneitz S, Rosenwald A, Scherer C, Spahn M, Burger M, et al. Combination of expression levels of miR-21 and miR-126 is associated with cancer-specific survival in clear-cell renal cell carcinoma. BMC Cancer. 2014;14:25.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Liang J, Zhang Y, Jiang G, Liu Z, Xiang W, Chen X, et al. MiR-138 induces renal carcinoma cell senescence by targeting EZH2 and is downregulated in human clear cell renal cell carcinoma. Oncol Res. 2014;21:83–91.CrossRefGoogle Scholar
  9. 9.
    Iwamoto H, Kanda Y, Sejima T, Osaki M, Okada F, Takenaka A. Serum miR-210 as a potential biomarker of early clear cell renal cell carcinoma. Int J Oncol. 2014;44:53–8.PubMedGoogle Scholar
  10. 10.
    Huang QB, Ma X, Zhang X, Liu SW, Ai Q, Shi TP, et al. Down-regulated miR-30a in clear cell renal cell carcinoma correlated with tumor hematogenous metastasis by targeting angiogenesis-specific DLL4. PLoS One. 2013;8:e67294.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Gebauer K, Peters I, Dubrowinskaja N, Hennenlotter J, Abbas M, Scherer R, et al. Hsa-mir-124-3 CpG island methylation is associated with advanced tumours and disease recurrence of patients with clear cell renal cell carcinoma. Br J Cancer. 2013;108:131–8.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Zhao A, Li G, Peoc’h M, Genin C, Gigante M. Serum miR-210 as a novel biomarker for molecular diagnosis of clear cell renal cell carcinoma. Exp Mol Pathol. 2013;94:115–20.PubMedCrossRefGoogle Scholar
  13. 13.
    Mikhaylova O, Stratton Y, Hall D, Kellner E, Ehmer B, Drew AF, et al. VHL-regulated MiR-204 suppresses tumor growth through inhibition of LC3B-mediated autophagy in renal clear cell carcinoma. Cancer Cell. 2012;21:532–46.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Valera VA, Walter BA, Linehan WM, Merino MJ. Regulatory effects of microRNA-92 (miR-92) on VHL gene expression and the hypoxic activation of miR-210 in clear cell renal cell carcinoma. J Cancer Educ. 2011;2:515–26.CrossRefGoogle Scholar
  15. 15.
    Song T, Zhang X, Wang C, Wu Y, Cai W, Gao J, et al. miR-138 suppresses expression of hypoxia-inducible factor 1alpha (HIF-1alpha) in clear cell renal cell carcinoma 786-O cells. Asian Pac J Cancer Prev. 2011;12:1307–11.PubMedGoogle Scholar
  16. 16.
    Hildebrandt MA, Gu J, Lin J, Ye Y, Tan W, Tamboli P, et al. Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. Oncogene. 2010;29:5724–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Omrani M, Hashemi M, Eskandari-Nasab E, Hasani SS, Mashhadi MA, Arbabi F, et al. hsa-miR-499 rs3746444 gene polymorphism is associated with susceptibility to breast cancer in an Iranian population. Biomark Med. 2014;8:259–67.PubMedCrossRefGoogle Scholar
  18. 18.
    Chae YS, Kim JG, Lee SJ, Kang BW, Lee YJ, Park JY, et al. A miR-146a polymorphism (rs2910164) predicts risk of and survival from colorectal cancer. Anticancer Res. 2013;33:3233–9.PubMedGoogle Scholar
  19. 19.
    Du W, Ma X, Kong W, Liu T, Wei B, Yu J, et al. Association between rs11614913 polymorphism in miR-196a2 and colorectal cancer risk: a meta-analysis. Cancer Biomark. 2013;13:457–64.PubMedGoogle Scholar
  20. 20.
    Lin Y, Nie Y, Zhao J, Chen X, Ye M, Li Y, et al. Genetic polymorphism at miR-181a binding site contributes to gastric cancer susceptibility. Carcinogenesis. 2012;33:2377–83.PubMedCrossRefGoogle Scholar
  21. 21.
    Wang F, Ma YL, Zhang P, Shen TY, Shi CZ, Yang YZ, et al. SP1 mediates the link between methylation of the tumour suppressor miR-149 and outcome in colorectal cancer. J Pathol. 2013;229:12–24.PubMedCrossRefGoogle Scholar
  22. 22.
    Bischoff A, Huck B, Keller B, Strotbek M, Schmid S, Boerries M, Busch H, Muller D, Olayioye MA: miR-149 functions as a tumor suppressor by controlling breast epithelial cell migration and invasion. Cancer Res 2014Google Scholar
  23. 23.
    Ke Y, Zhao W, Xiong J, Cao R. miR-149 inhibits non-small-cell lung cancer cells EMT by targeting FOXM1. Biochem res int. 2013;2013:506731.PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Lin RJ, Lin YC, Yu AL. miR-149* induces apoptosis by inhibiting Akt1 and E2F1 in human cancer cells. Mol Carcinog. 2010;49:719–27.PubMedGoogle Scholar
  25. 25.
    Ding SL, Wang JX, Jiao JQ, Tu X, Wang Q, Liu F, et al. A pre-microRNA-149 (miR-149) genetic variation affects miR-149 maturation and its ability to regulate the Puma protein in apoptosis. J Biol Chem. 2013;288:26865–77.PubMedCentralPubMedCrossRefGoogle Scholar
  26. 26.
    Mori M, Triboulet R, Mohseni M, Schlegelmilch K, Shrestha K, Camargo FD, et al. Hippo signaling regulates microprocessor and links cell-density-dependent miRNA biogenesis to cancer. Cell. 2014;156:893–906.PubMedCrossRefGoogle Scholar
  27. 27.
    Sozzi G, Boeri M, Rossi M, Verri C, Suatoni P, Bravi F, et al. Clinical utility of a plasma-based miRNA signature classifier within computed tomography lung cancer screening: a correlative mild trial study. J Clin Oncol. 2014;32:768–73.PubMedCrossRefGoogle Scholar
  28. 28.
    Heneghan HM, Miller N, Kerin MJ: Circulating miRNA signatures: promising prognostic tools for cancer. J Clin Oncol 2010;28:e573-574; author reply e575-576.Google Scholar
  29. 29.
    Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, et al. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 2009;138:592–603.PubMedCentralPubMedCrossRefGoogle Scholar
  30. 30.
    Ruvkun G. Clarifications on miRNA and cancer. Science. 2006;311:36–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Mezzanzanica D, Canevari S, Cecco LD, Bagnoli M. miRNA control of apoptotic programs: focus on ovarian cancer. Expert Rev Mol Diagn. 2011;11:277–86.PubMedGoogle Scholar
  32. 32.
    Wang Y, Zhang X, Li H, Yu J, Ren X. The role of miRNA-29 family in cancer. Eur J Cell Biol. 2013;92:123–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Zadran S, Remacle F, Levine RD. miRNA and mRNA cancer signatures determined by analysis of expression levels in large cohorts of patients. Proc Natl Acad Sci U S A. 2013;110:19160–5.PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Zhigang Wang
    • 1
  • Meng Wei
    • 1
  • Yi Ren
    • 2
  • Hua Liu
    • 2
  • Meng Wang
    • 2
  • Kehui Shi
    • 2
  • Hongli Jiang
    • 3
  1. 1.School of Medicine Dialysis Center of First Affiliated Hospital of Medicine SchoolXi’an Jiaotong UniversityXi’anChina
  2. 2.Department of Nephrology Dialysis Center First Affiliated Hospital of Medicine SchoolXi’an Jiaotong UniversityXi’anChina
  3. 3.Dialysis Center of First Affiliated Hospital of Medicine SchoolXi’an Jiaotong UniversityXi’anChina

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