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Article

miR‑31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1

  • Authors:
    • Chenghuan Hu
    • Feizhou Huang
    • Gang Deng
    • Wanpin Nie
    • Wei Huang
    • Xi Zeng
  • View Affiliations / Copyright

    Affiliations: Department of Hepatobiliary and Pancreatic Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
  • Pages: 1265-1270
    |
    Published online on: September 18, 2013
       https://doi.org/10.3892/etm.2013.1311
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Abstract

MicroRNAs (miRNAs) are involved in the pathogenesis of intrahepatic cholangiocarcinoma (ICC). However, the role of microRNA‑31 (miR‑31) in ICC has yet to be elucidated. In this study, we demonstrated that the expression of miR‑31 was significantly upregulated in ICC tissues and the human ICC cell line HCCC‑9810, when compared with that in normal adjacent tissues. Bioinformatic analysis and a dual‑luciferase reporter assay revealed RAS p21 GTPase activating protein 1 (RASA1) to be a direct target of miR‑31 in HCCC‑9810 cells. Further investigation showed that the protein expression level of RASA1 was significantly decreased in ICC tissues, suggesting an inverse correlation between miR‑31 and RASA1 expression during the tumorigenesis of ICC. Moreover, the forced downregulation of miR‑31 by its inhibitor in HCCC‑9810 cells significantly inhibited cell proliferation and promoted cell apoptosis. However, when the cells were cotransfected with miR‑31 inhibitor and RASA1‑specific small interfering RNA (siRNA), these changes were attenuated. Further analysis of the molecular mechanism showed that the activity of the RAS‑mitogen-activated protein kinase (MAPK) signaling pathway was significantly decreased in miR‑31‑downregulated HCCC‑8910 cells, while cotransfection with miR‑31 inhibitor and RASA1‑specific siRNA attenuated this effect. These results indicate that the downregulation of RASA1 by miR‑31 promoted cellular proliferation and inhibited cellular apoptosis, partially by upregulating the activity of the RAS‑MAPK signaling pathway in ICC. In conclusion, the present study revealed important regulatory functions of miR‑31 and RASA1 in ICC, indicating that miR‑31 and RASA1 may become promising diagnostic and/or therapeutic targets for ICC.
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1. 

Farges O and Fuks D: Clinical presentation and management of intrahepatic cholangiocarcinoma. Gastroenterol Clin Biol. 34:191–199. 2010. View Article : Google Scholar

2. 

Luh F, Kuei A, Fann P, Chu P and Yen Y: Intrahepatic cholangiocarcinoma and hepatitis: case study and literature review. Anticancer Res. 29:3239–3243. 2009.PubMed/NCBI

3. 

Sempoux C, Jibara G, Ward SC, et al: Intrahepatic cholangiocarcinoma: new insights in pathology. Semin Liver Dis. 31:49–60. 2011. View Article : Google Scholar : PubMed/NCBI

4. 

Isomoto H: Epigenetic alterations associated with cholangiocarcinoma (review). Oncol Rep. 22:227–232. 2009.PubMed/NCBI

5. 

Zhou L, Yang ZX, Song WJ, et al: MicroRNA-21 regulates the migration and invasion of a stem-like population in hepatocellular carcinoma. Int J Oncol. 43:661–669. 2013.PubMed/NCBI

6. 

Guo P, Lan J, Ge J, Nie Q, Mao Q and Qiu Y: miR-708 acts as a tumor suppressor in human glioblastoma cells. Oncol Rep. 30:870–876. 2013.PubMed/NCBI

7. 

Brunet Vega A, Pericay C, Moya I, et al: microRNA expression profile in stage III colorectal cancer: Circulating miR-18a and miR-29a as promising biomarkers. Oncol Rep. 30:320–326. 2013.PubMed/NCBI

8. 

Karakatsanis A, Papaconstantinou I, Gazouli M, Lyberopoulou A, Polymeneas G and Voros D: Expression of microRNAs, miR-21, miR-31, miR-122, miR-145, miR-146a, miR-200c, miR-221, miR-222, and miR-223 in patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma and its prognostic significance. Mol Carcinog. 52:297–303. 2013. View Article : Google Scholar

9. 

Oishi N, Kumar MR, Roessler S, et al: Transcriptomic profiling reveals hepatic stem-like gene signatures and interplay of miR-200c and epithelial-mesenchymal transition in intrahepatic cholangiocarcinoma. Hepatology. 56:1792–1803. 2012. View Article : Google Scholar

10. 

Zeng B, Li Z, Chen R, et al: Epigenetic regulation of miR-124 by hepatitis C virus core protein promotes migration and invasion of intrahepatic cholangiocarcinoma cells by targeting SMYD3. FEBS Lett. 586:3271–3278. 2012. View Article : Google Scholar

11. 

Boon LM, Mulliken JB and Vikkula M: RASA1: variable phenotype with capillary and arteriovenous malformations. Curr Opin Genet Dev. 15:265–269. 2005. View Article : Google Scholar : PubMed/NCBI

12. 

Sun D, Yu F, Ma Y, et al: MicroRNA-31 activates the RAS pathway and functions as an oncogenic MicroRNA in human colorectal cancer by repressing RAS p21 GTPase activating protein 1 (RASA1). J Biol Chem. 288:9508–9518. 2013. View Article : Google Scholar : PubMed/NCBI

13. 

Calvisi DF, Ladu S, Conner EA, et al: Inactivation of Ras GTPase-activating proteins promotes unrestrained activity of wild-type Ras in human liver cancer. J Hepatol. 54:311–319. 2011. View Article : Google Scholar : PubMed/NCBI

14. 

Hu X, Stern HM, Ge L, et al: Genetic alterations and oncogenic pathways associated with breast cancer subtypes. Mol Cancer Res. 7:511–522. 2009. View Article : Google Scholar : PubMed/NCBI

15. 

Ulger C, Toruner GA, Alkan M, et al: Comprehensive genome-wide comparison of DNA and RNA level scan using microarray technology for identification of candidate cancer-related genes in the HL-60 cell line. Cancer Genet Cytogenet. 147:28–35. 2003. View Article : Google Scholar : PubMed/NCBI

16. 

Yang XY, Guan M, Vigil D, Der CJ, Lowy DR and Popescu NC: p120Ras-GAP binds the DLC1 Rho-GAP tumor suppressor protein and inhibits its RhoA GTPase and growth-suppressing activities. Oncogene. 28:1401–1409. 2009. View Article : Google Scholar : PubMed/NCBI

17. 

John B, Enright AJ, Aravin A, Tuschl T, Sander C and Marks DS: Human MicroRNA targets. PLoS Biol. 2:e3632004. View Article : Google Scholar

18. 

Dweep H, Sticht C, Pandey P and Gretz N: miRWalk-database: prediction of possible miRNA binding sites by ‘walking’ the genes of three genomes. J Biomed Inform. 44:839–847. 2011.

19. 

Rehmsmeier M, Steffen P, Hochsmann M and Giegerich R: Fast and effective prediction of microRNA/target duplexes. RNA. 10:1507–1517. 2004. View Article : Google Scholar : PubMed/NCBI

20. 

Krek A, Grün D, Poy MN, et al: Combinatorial microRNA target predictions. Nat Genet. 37:495–500. 2005. View Article : Google Scholar

21. 

Lewis BP, Shih IH, Jones-Rhoades MW, Bartel DP and Burge CB: Prediction of mammalian microRNA targets. Cell. 115:787–798. 2003. View Article : Google Scholar : PubMed/NCBI

22. 

Lapinski PE, Qiao Y, Chang CH and King PD: A role for p120 RasGAP in thymocyte positive selection and survival of naive T cells. J Immunol. 187:151–163. 2011. View Article : Google Scholar : PubMed/NCBI

23. 

Osman MA, Sarkar FH and Rodriguez-Boulan E: A molecular rheostat at the interface of cancer and diabetes. Biochim Biophys Acta. 1836:166–176. 2013.PubMed/NCBI

24. 

Kawahigashi Y, Mishima T, Mizuguchi Y, et al: MicroRNA profiling of human intrahepatic cholangiocarcinoma cell lines reveals biliary epithelial cell-specific microRNAs. J Nippon Med Sch. 76:188–197. 2009. View Article : Google Scholar : PubMed/NCBI

25. 

Chen L, Yan HX, Yang W, et al: The role of microRNA expression pattern in human intrahepatic cholangiocarcinoma. J Hepatol. 50:358–369. 2009. View Article : Google Scholar : PubMed/NCBI

26. 

Xu RS, Wu XD, Zhang SQ, et al: The tumor suppressor gene RhoBTB1 is a novel target of miR-31 in human colon cancer. Int J Oncol. 42:676–682. 2013.PubMed/NCBI

27. 

Tu HF, Lin SC and Chang KW: MicroRNA aberrances in head and neck cancer: pathogenetic and clinical significance. Curr Opin Otolaryngol Head Neck Surg. 21:104–111. 2013. View Article : Google Scholar : PubMed/NCBI

28. 

Liu CJ, Lin SC, Yang CC, Cheng HW and Chang KW: Exploiting salivary miR-31 as a clinical biomarker of oral squamous cell carcinoma. Head Neck. 34:219–224. 2012. View Article : Google Scholar : PubMed/NCBI

29. 

Zhang Y, Guo J, Li D, et al: Down-regulation of miR-31 expression in gastric cancer tissues and its clinical significance. Med Oncol. 27:685–689. 2010. View Article : Google Scholar : PubMed/NCBI

30. 

Schaefer A, Jung M, Mollenkopf HJ, et al: Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer. 126:1166–1176. 2010.PubMed/NCBI

31. 

Creighton CJ, Fountain MD, Yu Z, et al: Molecular profiling uncovers a p53-associated role for microRNA-31 in inhibiting the proliferation of serous ovarian carcinomas and other cancers. Cancer Res. 70:1906–1915. 2010. View Article : Google Scholar : PubMed/NCBI

32. 

Lu Z, Ye Y, Jiao D, Qiao J, Cui S and Liu Z: miR-155 and miR-31 are differentially expressed in breast cancer patients and are correlated with the estrogen receptor and progesterone receptor status. Oncol Lett. 4:1027–1032. 2012.

33. 

Veerla S, Lindgren D, Kvist A, et al: MiRNA expression in urothelial carcinomas: important roles of miR-10a, miR-222, miR-125b, miR-7 and miR-452 for tumor stage and metastasis, and frequent homozygous losses of miR-31. Int J Cancer. 124:2236–2242. 2009. View Article : Google Scholar : PubMed/NCBI

34. 

Wang C, Cigliano A, Delogu S, et al: Functional crosstalk between AKT/mTOR and Ras/MAPK pathways in hepatocarcinogenesis: Implications for the treatment of human liver cancer. Cell Cycle. 12:1999–2010. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Hu C, Huang F, Deng G, Nie W, Huang W and Zeng X: miR‑31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1. Exp Ther Med 6: 1265-1270, 2013.
APA
Hu, C., Huang, F., Deng, G., Nie, W., Huang, W., & Zeng, X. (2013). miR‑31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1. Experimental and Therapeutic Medicine, 6, 1265-1270. https://doi.org/10.3892/etm.2013.1311
MLA
Hu, C., Huang, F., Deng, G., Nie, W., Huang, W., Zeng, X."miR‑31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1". Experimental and Therapeutic Medicine 6.5 (2013): 1265-1270.
Chicago
Hu, C., Huang, F., Deng, G., Nie, W., Huang, W., Zeng, X."miR‑31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1". Experimental and Therapeutic Medicine 6, no. 5 (2013): 1265-1270. https://doi.org/10.3892/etm.2013.1311
Copy and paste a formatted citation
x
Spandidos Publications style
Hu C, Huang F, Deng G, Nie W, Huang W and Zeng X: miR‑31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1. Exp Ther Med 6: 1265-1270, 2013.
APA
Hu, C., Huang, F., Deng, G., Nie, W., Huang, W., & Zeng, X. (2013). miR‑31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1. Experimental and Therapeutic Medicine, 6, 1265-1270. https://doi.org/10.3892/etm.2013.1311
MLA
Hu, C., Huang, F., Deng, G., Nie, W., Huang, W., Zeng, X."miR‑31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1". Experimental and Therapeutic Medicine 6.5 (2013): 1265-1270.
Chicago
Hu, C., Huang, F., Deng, G., Nie, W., Huang, W., Zeng, X."miR‑31 promotes oncogenesis in intrahepatic cholangiocarcinoma cells via the direct suppression of RASA1". Experimental and Therapeutic Medicine 6, no. 5 (2013): 1265-1270. https://doi.org/10.3892/etm.2013.1311
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