Advertisement

Medical Oncology

, 31:230 | Cite as

MicroRNA-130a is down-regulated in hepatocellular carcinoma and associates with poor prognosis

  • Binkui Li
  • Pinzhu Huang
  • Jiliang Qiu
  • Yadi Liao
  • Jian Hong
  • Yunfei Yuan
Original Paper

Abstract

MicroRNA-130a (miR-130a) has recently been found to be implicated in many critical processes in various types of human cancer. However, the prognostic value of miR-130a in hepatocellular carcinoma (HCC) remains unclear. In the present study, we investigated the expression of miR-130a in HCC and analyzed its association with clinical features and prognosis of HCC patients. We determined the expression level of miR-130a in 102 cases of paired HCC and adjacent non-tumor tissues by quantitative real-time PCR (qRT-PCR). The qRT-PCR results showed that the miR-130a expression was significantly down-regulated in tumor tissues compared with the adjacent non-tumor tissues (P < 0.001). Correlation analysis showed that miR-130a expression was significantly correlated with gender (P = 0.008), HBsAg status (P = 0.038), tumor size (P = 0.003), and tumor-node-metastasis stage (P = 0.029). Kaplan–Meier analysis showed that patients with low miR-130a expression had a poorer overall survival than patients with high miR-130a expression (log-rank P = 0.007). The multivariate Cox regression analysis indicated that miR-130a expression was an independent prognostic factor for overall survival (hazard ratio 2.217; 95 % CI 1.103–4.458; P = 0.025). The present study showed for the first time that miR-130a expression was significantly down-regulated in HCC and associated with overall survival of patients with HCC. The present study also provided evidence that miR-130a was an independent prognostic factor and could serve as a potential prognostic biomarker for patients with HCC.

Keywords

miR-130a Hepatocellular carcinoma Real-time PCR Prognosis 

Notes

Acknowledgments

This work was supported in part by grants from the National Natural Science Foundation of China (81101863 and 81172344), Guangdong Natural Science Foundation (S2011040004570), and the Fundamental Research Funds for the Central Universities (11ykpy60).

Conflict of interest

None.

References

  1. 1.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29. doi: 10.3322/caac.21208.PubMedCrossRefGoogle Scholar
  2. 2.
    Schwartz M, Roayaie S, Konstadoulakis M. Strategies for the management of hepatocellular carcinoma. Nat Clin Pract Oncol. 2007;4(7):424–32. doi: 10.1038/ncponc0844.PubMedCrossRefGoogle Scholar
  3. 3.
    Poon RT, Fan ST. Hepatectomy for hepatocellular carcinoma: patient selection and postoperative outcome. Liver Transpl. 2004;10(2 Suppl 1):S39–45. doi: 10.1002/lt.20040.PubMedCrossRefGoogle Scholar
  4. 4.
    Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology. 2004;127(5 Suppl 1):S5–16.PubMedCrossRefGoogle Scholar
  5. 5.
    Portolani N, Coniglio A, Ghidoni S, Giovanelli M, Benetti A, Tiberio GA, et al. Early and late recurrence after liver resection for hepatocellular carcinoma: prognostic and therapeutic implications. Ann Surg. 2006;243(2):229–35. doi: 10.1097/01.sla.0000197706.21803.a1.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Sobin LH, Compton CC. TNM seventh edition: what’s new, what’s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer. 2010;116(22):5336–9. doi: 10.1002/cncr.25537.PubMedCrossRefGoogle Scholar
  7. 7.
    Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis. 2010;30(1):61–74. doi: 10.1055/s-0030-1247133.PubMedCrossRefGoogle Scholar
  8. 8.
    Bruix J, Gores GJ, Mazzaferro V. Hepatocellular carcinoma: clinical frontiers and perspectives. Gut. 2014;63(5):844–55. doi: 10.1136/gutjnl-2013-306627.PubMedCrossRefGoogle Scholar
  9. 9.
    Lee SC, Tan HT, Chung MC. Prognostic biomarkers for prediction of recurrence of hepatocellular carcinoma: current status and future prospects. World J Gastroenterol. 2014;20(12):3112–24. doi: 10.3748/wjg.v20.i12.3112.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Aravalli RN, Steer CJ, Cressman EN. Molecular mechanisms of hepatocellular carcinoma. Hepatology. 2008;48(6):2047–63. doi: 10.1002/hep.22580.PubMedCrossRefGoogle Scholar
  11. 11.
    Kong YW, Ferland-McCollough D, Jackson TJ, Bushell M. microRNAs in cancer management. Lancet Oncol. 2012;13(6):e249–58. doi: 10.1016/S1470-2045(12)70073-6.PubMedCrossRefGoogle Scholar
  12. 12.
    Chaiteerakij R, Addissie BD, Roberts LR. Update on biomarkers of hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2013;. doi: 10.1016/j.cgh.2013.10.038.PubMedGoogle Scholar
  13. 13.
    Zhao YJ, Ju Q, Li GC. Tumor markers for hepatocellular carcinoma. Mol Clin Oncol. 2013;1(4):593–8. doi: 10.3892/mco.2013.119.PubMedPubMedCentralGoogle Scholar
  14. 14.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.PubMedCrossRefGoogle Scholar
  15. 15.
    Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66. doi: 10.1038/nrc1997.PubMedCrossRefGoogle Scholar
  16. 16.
    Giordano S, Columbano A. MicroRNAs: new tools for diagnosis, prognosis, and therapy in hepatocellular carcinoma? Hepatology. 2013;57(2):840–7. doi: 10.1002/hep.26095.PubMedCrossRefGoogle Scholar
  17. 17.
    Chen Y, Gorski DH. Regulation of angiogenesis through a microRNA (miR-130a) that down-regulates antiangiogenic homeobox genes GAX and HOXA5. Blood. 2008;111(3):1217–26. doi: 10.1182/blood-2007-07-104133.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Acunzo M, Visone R, Romano G, Veronese A, Lovat F, Palmieri D, et al. miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222. Oncogene. 2012;31(5):634–42. doi: 10.1038/onc.2011.260.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Yang L, Li N, Wang H, Jia X, Wang X, Luo J. Altered microRNA expression in cisplatin-resistant ovarian cancer cells and upregulation of miR-130a associated with MDR1/P-glycoprotein-mediated drug resistance. Oncol Rep. 2012;28(2):592–600. doi: 10.3892/or.2012.1823.PubMedGoogle Scholar
  20. 20.
    Zhang X, Huang L, Zhao Y, Tan W. Downregulation of miR-130a contributes to cisplatin resistance in ovarian cancer cells by targeting X-linked inhibitor of apoptosis (XIAP) directly. Acta Biochim Biophys Sin. 2013;45(12):995–1001. doi: 10.1093/abbs/gmt113.PubMedCrossRefGoogle Scholar
  21. 21.
    Zhou YM, Liu J, Sun W. MiR-130a overcomes gefitinib resistance by targeting met in non-small cell lung cancer cell lines. Asian Pac J Cancer Prev. 2014;15(3):1391–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Xu N, Shen C, Luo Y, Xia L, Xue F, Xia Q, et al. Upregulated miR-130a increases drug resistance by regulating RUNX3 and Wnt signaling in cisplatin-treated HCC cell. Biochem Biophys Res Commun. 2012;425(2):468–72. doi: 10.1016/j.bbrc.2012.07.127.PubMedCrossRefGoogle Scholar
  23. 23.
    Calin GA, Ferracin M, Cimmino A, Di Leva G, Shimizu M, Wojcik SE, et al. A MicroRNA signature associated with prognosis and progression in chronic lymphocytic leukemia. N Engl J Med. 2005;353(17):1793–801. doi: 10.1056/NEJMoa050995.PubMedCrossRefGoogle Scholar
  24. 24.
    Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9(3):189–98. doi: 10.1016/j.ccr.2006.01.025.PubMedCrossRefGoogle Scholar
  25. 25.
    Li Y, Tan W, Neo TW, Aung MO, Wasser S, Lim SG, et al. Role of the miR-106b-25 microRNA cluster in hepatocellular carcinoma. Cancer Sci. 2009;100(7):1234–42. doi: 10.1111/j.1349-7006.2009.01164.x.PubMedCrossRefGoogle Scholar
  26. 26.
    Wei R, Huang GL, Zhang MY, Li BK, Zhang HZ, Shi M, et al. Clinical significance and prognostic value of microRNA expression signatures in hepatocellular carcinoma. Clin Cancer Res. 2013;19(17):4780–91. doi: 10.1158/1078-0432.CCR-12-2728.PubMedCrossRefGoogle Scholar
  27. 27.
    Shen G, Jia H, Tai Q, Li Y, Chen D. miR-106b downregulates adenomatous polyposis coli and promotes cell proliferation in human hepatocellular carcinoma. Carcinogenesis. 2013;34(1):211–9. doi: 10.1093/carcin/bgs320.PubMedCrossRefGoogle Scholar
  28. 28.
    Liu L, Nie J, Chen L, Dong G, Du X, Wu X, et al. The oncogenic role of microRNA-130a/301a/454 in human colorectal cancer via targeting Smad4 expression. PLoS ONE. 2013;8(2):e55532. doi: 10.1371/journal.pone.0055532.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Qiu S, Lin S, Hu D, Feng Y, Tan Y, Peng Y. Interactions of miR-323/miR-326/miR-329 and miR-130a/miR-155/miR-210 as prognostic indicators for clinical outcome of glioblastoma patients. J Transl Med. 2013;11:10. doi: 10.1186/1479-5876-11-10.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Boll K, Reiche K, Kasack K, Morbt N, Kretzschmar AK, Tomm JM, et al. MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma. Oncogene. 2013;32(3):277–85. doi: 10.1038/onc.2012.55.PubMedCrossRefGoogle Scholar
  31. 31.
    Kovaleva V, Mora R, Park YJ, Plass C, Chiramel AI, Bartenschlager R, et al. miRNA-130a targets ATG2B and DICER1 to inhibit autophagy and trigger killing of chronic lymphocytic leukemia cells. Cancer Res. 2012;72(7):1763–72. doi: 10.1158/0008-5472.CAN-11-3671.PubMedCrossRefGoogle Scholar
  32. 32.
    Liu WH, Yeh SH, Lu CC, Yu SL, Chen HY, Lin CY, et al. MicroRNA-18a prevents estrogen receptor-alpha expression, promoting proliferation of hepatocellular carcinoma cells. Gastroenterology. 2009;136(2):683–93. doi: 10.1053/j.gastro.2008.10.029.PubMedCrossRefGoogle Scholar
  33. 33.
    Li CL, Yeh KH, Liu WH, Chen CL, Chen DS, Chen PJ, et al. Elevated p53 promotes the processing of miR-18a to decrease estrogen receptor-alpha in female hepatocellular carcinoma. Int J Cancer. 2014;. doi: 10.1002/ijc.29052.Google Scholar
  34. 34.
    Zhang X, Daucher M, Armistead D, Russell R, Kottilil S. MicroRNA expression profiling in HCV-infected human hepatoma cells identifies potential anti-viral targets induced by interferon-alpha. PLoS ONE. 2013;8(2):e55733. doi: 10.1371/journal.pone.0055733.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Binkui Li
    • 1
    • 2
  • Pinzhu Huang
    • 1
    • 2
  • Jiliang Qiu
    • 1
    • 2
  • Yadi Liao
    • 1
    • 2
  • Jian Hong
    • 1
    • 2
  • Yunfei Yuan
    • 1
    • 2
  1. 1.State Key Laboratory of Oncology in South ChinaGuangzhouChina
  2. 2.Department of Hepatobiliary OncologySun Yat-sen University Cancer CenterGuangzhouChina

Personalised recommendations