Prognostic significance of Dicer expression in hepatocellular carcinoma

Zhang,Li; Wang,Cuiju; Liu,Shufeng; Zhao,Yufei; Liu,Chao; Guo,Zhanjun

doi:10.3892/ol.2016.4547

Prognostic significance of Dicer expression in hepatocellular carcinoma

Authors:
- Li Zhang
- Cuiju Wang
- Shufeng Liu
- Yufei Zhao
- Chao Liu
- Zhanjun Guo
View Affiliations

Affiliations: Hebei Key Lab of Animal Science, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Gynecology Ultrasound, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
Published online on: May 9, 2016 https://doi.org/10.3892/ol.2016.4547
Pages: 3961-3966
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Dicer is a RNaseIII endonuclease of the microRNA processing pathway, which is implicated in carcinogenesis of various types of human cancer. The present study assessed the expression level of Dicer in hepatocellular carcinoma (HCC) tissue to evaluate its association with HCC tumorigenesis. A low expression of Dicer was significantly associated with a shorter postoperative survival time of patients with HCC, which was assessed using the log‑rank test with Kaplan‑Meier survival analysis. Multivariate analysis identified that Dicer expression was an independent predictor for HCC outcome (relative risk, 0.660; 95% confidence interval, 0.506‑0.861; P=0.002). A functional assay demonstrated that Dicer overexpression inhibited the proliferation and promoted the apoptosis of HCC cells. In addition, a Transwell assay revealed that Dicer markedly inhibited the migration and invasion of HCC cells. The present findings indicate that Dicer expression modified the outcomes of HCC patients by inhibiting proliferation, promoting apoptosis and inhibiting metastasis of HCC cells.

View Figures

View References

1	Gomaa AI, Khan SA, Toledano MB, Waked I and Taylor-Robinson SD: Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis. World J Gastroenterol. 14:4300–4308. 2008. View Article : Google Scholar : PubMed/NCBI
2	Guo Z, Wu C, Wang X, Wang C, Zhang R and Shan B: A polymorphism at the miR-502 binding site in the 3′-untranslated region of the histone methyltransferase SET8 is associated with hepatocellular carcinoma outcome. Int J Cancer. 131:1318–1322. 2012. View Article : Google Scholar : PubMed/NCBI
3	Guo Z, Li LQ, Jiang JH, Ou C, Zeng LX and Xiang BD: Cancer stem cell markers correlate with early recurrence and survival in hepatocellular carcinoma. World J Gastroenterol. 20:2098–2106. 2014. View Article : Google Scholar : PubMed/NCBI
4	Li X, Yang W, Lou L, Chen Y, Wu S and Ding G: MicroRNA: A promising diagnostic biomarker and therapeutic target for hepatocellular carcinoma. Dig Dis Sci. 59:1099–1107. 2014. View Article : Google Scholar : PubMed/NCBI
5	Minagawa M, Makuuchi M, Takayama T and Kokudo N: Selection criteria for repeat hepatectomy in patients with recurrent hepatocellular carcinoma. Ann Surg. 238:703–710. 2003. View Article : Google Scholar : PubMed/NCBI
6	Callegari E, Gramantieri L, Domenicali M, D'Abundo L, Sabbioni S and Negrini M: MicroRNAs in liver cancer: A model for investigating pathogenesis and novel therapeutic approaches. Cell Death Differ. 22:46–57. 2015. View Article : Google Scholar : PubMed/NCBI
7	Lee RC, Feinbaum RL and Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75:843–854. 1993. View Article : Google Scholar : PubMed/NCBI
8	Bagga S, Bracht J, Hunter S, Massirer K, Holtz J, Eachus R and Pasquinelli AE: Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell. 122:553–563. 2005. View Article : Google Scholar : PubMed/NCBI
9	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
10	Kuehbacher A, Urbich C, Zeiher AM and Dimmeler S: Role of Dicer and Drosha for endothelial microRNA expression and angiogenesis. Circ Res. 101:59–68. 2007. View Article : Google Scholar : PubMed/NCBI
11	Barbato C, Ciotti MT, Serafino A, Calissano P and Cogoni C: Dicer expression and localization in post-mitotic neurons. Brain Res. 1175:17–27. 2007. View Article : Google Scholar : PubMed/NCBI
12	Cochrane DR, Cittelly DM, Howe EN, Spoelstra NS, McKinsey EL, LaPara K, Elias A, Yee D and Richer JK: MicroRNAs link estrogen receptor alpha status and Dicer levels in breast cancer. Horm Cancer. 1:306–319. 2010. View Article : Google Scholar : PubMed/NCBI
13	Dedes KJ, Natrajan R, Lambros MB, Geyer FC, Lopez-Garcia MA, Savage K, Jones RL and Reis-Filho JS: Down-regulation of the miRNA master regulators Drosha and Dicer is associated with specific subgroups of breast cancer. Eur J Cancer. 47:138–150. 2011. View Article : Google Scholar : PubMed/NCBI
14	Yan M, Huang HY, Wang T, Wan Y, Cui SD, Liu ZZ and Fan QX: Dysregulated expression of Dicer and drosha in breast cancer. Pathol Oncol Res. 18:343–348. 2012. View Article : Google Scholar : PubMed/NCBI
15	Caffrey E, Ingoldsby H, Wall D, Webber M, Dinneen K, Murillo LS, Inderhaug C, Newell J, Gupta S and Callagy G: Prognostic significance of deregulated Dicer expression in breast cancer. PLoS One. 8:e837242013. View Article : Google Scholar : PubMed/NCBI
16	Karube Y, Tanaka H, Osada H, Tomida S, Tatematsu Y, Yanagisawa K, Yatabe Y, Takamizawa J, Miyoshi S, Mitsudomi T and Takahashi T: Reduced expression of Dicer associated with poor prognosis in lung cancer patients. Cancer Sci. 96:111–115. 2005. View Article : Google Scholar : PubMed/NCBI
17	Merritt WM, Lin YG, Han LY, Kamat AA, Spannuth WA, Schmandt R, Urbauer D, Pennacchio LA, Cheng JF, Nick AM, et al: Dicer, Drosha, and outcomes in patients with ovarian cancer. N Engl J Med. 359:2641–2650. 2008. View Article : Google Scholar : PubMed/NCBI
18	Köbel M, Gilks CB and Huntsman DG: Dicer and Drosha in ovarian cancer. N Engl J Med. 360:1150–1151; author reply 1151. 2009. View Article : Google Scholar : PubMed/NCBI
19	Pampalakis G, Diamandis EP, Katsaros D and Sotiropoulou G: Down-regulation of Dicer expression in ovarian cancer tissues. Clin Biochem. 43:324–327. 2010. View Article : Google Scholar : PubMed/NCBI
20	Lin RJ, Lin YC, Chen J, Kuo HH, Chen YY, Diccianni MB, London WB, Chang CH and Yu AL: MicroRNA signature and expression of Dicer and Drosha can predict prognosis and delineate risk groups in neuroblastoma. Cancer Res. 70:7841–7850. 2010. View Article : Google Scholar : PubMed/NCBI
21	Zeng S, Yang J, Zhao J, Liu Q, Rong M, Guo Z and Gao W: Silencing Dicer expression enhances cellular proliferative and invasive capacities in human tongue squamous cell carcinoma. Oncol Rep. 31:867–873. 2014.PubMed/NCBI
22	Zhu DX, Fan L, Lu RN, Fang C, Shen WY, Zou ZJ, Wang YH, Zhu HY, Miao KR, Liu P, et al: Downregulated Dicer expression predicts poor prognosis in chronic lymphocytic leukemia. Cancer Sci. 103:875–881. 2012. View Article : Google Scholar : PubMed/NCBI
23	Guo X, Liao Q, Chen P, Li X, Xiong W, Ma J, Li X, Luo Z, Tang H, Deng M, et al: The microRNA-processing enzymes: Drosha and Dicer can predict prognosis of nasopharyngeal carcinoma. J Cancer Res Clin Oncol. 138:49–56. 2012. View Article : Google Scholar : PubMed/NCBI
24	Wu JF, Shen W, Liu NZ, Zeng GL, Yang M, Zuo GQ, Gan XN, Ren H and Tang KF: Down-regulation of Dicer in hepatocellular carcinoma. Med Oncol. 28:804–809. 2011. View Article : Google Scholar : PubMed/NCBI
25	Kitagawa N, Ojima H, Shirakihara T, Shimizu H, Kokubu A, Urushidate T, Totoki Y, Kosuge T, Miyagawa S and Shibata T: Downregulation of the microRNA biogenesis components and its association with poor prognosis in hepatocellular carcinoma. Cancer Sci. 104:543–551. 2013. View Article : Google Scholar : PubMed/NCBI
26	Edge SB, Byrd DR and Compton CC: The American Joint Committee on Cancer: The 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 17:1471–1474. 2010. View Article : Google Scholar : PubMed/NCBI
27	Singh M, Zaino RJ, Filiaci VJ and Leslie KK: Relationship of estrogen and progesterone receptors to clinical outcome in metastatic endometrial carcinoma: A Gynecologic oncology group study. Gynecol Oncol. 106:325–333. 2007. View Article : Google Scholar : PubMed/NCBI
28	Yang M and Zhou H: Grass carp transforming growth factor-beta 1 (TGF-beta 1): Molecular cloning, tissue distribution and immunobiological activity in teleost peripheral blood lymphocytes. Mol Immunol. 45:1792–1798. 2008. View Article : Google Scholar : PubMed/NCBI
29	Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC and Williams R: Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 60:646–649. 1973. View Article : Google Scholar : PubMed/NCBI
30	Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, et al: MicroRNA expression profiles classify human cancers. Nature. 435:834–838. 2005. View Article : Google Scholar : PubMed/NCBI
31	Jafarnejad SM, Ardekani GS, Ghaffari M, Martinka M and Li G: Sox4-mediated Dicer expression is critical for suppression of melanoma cell invasion. Oncogene. 32:2131–2139. 2013. View Article : Google Scholar : PubMed/NCBI
32	Kuang Y, Cai J, Li D, Han Q, Cao J and Wang Z: Repression of Dicer is associated with invasive phenotype and chemoresistance in ovarian cancer. Oncol Lett. 5:1149–1154. 2013.PubMed/NCBI
33	Bian XJ, Zhang GM, Gu CY, Cai Y, Wang CF, Shen YJ, Zhu Y, Zhang HL, Dai B and Ye DW: Down-regulation of Dicer and Ago2 is associated with cell proliferation and apoptosis in prostate cancer. Tumour Biol. 35:11571–11578. 2014. View Article : Google Scholar : PubMed/NCBI
34	Faber C, Horst D, Hlubek F and Kirchner T: Overexpression of Dicer predicts poor survival in colorectal cancer. Eur J Cancer. 47:1414–1419. 2011. View Article : Google Scholar : PubMed/NCBI
35	Faggad A, Budczies J, Tchernitsa O, Darb-Esfahani S, Sehouli J, Müller BM, Wirtz R, Chekerov R, Weichert W, Sinn B, et al: Prognostic significance of Dicer expression in ovarian cancer-link to global microRNA changes and oestrogen receptor expression. J Pathol. 220:382–391. 2010.PubMed/NCBI
36	Gao C, Li X, Tong B, Wu K, Liu Y, Anniko M and Duan M: Up-regulated expression of Dicer reveals poor prognosis in laryngeal squamous cell carcinoma. Acta Otolaryngol. 134:959–963. 2014. View Article : Google Scholar : PubMed/NCBI
37	Nakagawa A, Shi Y, Kage-Nakadai E, Mitani S and Xue D: Caspase-dependent conversion of Dicer ribonuclease into a death-promoting deoxyribonuclease. Science. 328:327–334. 2010. View Article : Google Scholar : PubMed/NCBI
38	Krill KT, Gurdziel K, Heaton JH, Simon DP and Hammer GD: Dicer deficiency reveals microRNAs predicted to control gene expression in the developing adrenal cortex. Mol Endocrinol. 27:754–768. 2013. View Article : Google Scholar : PubMed/NCBI
39	Wu YY, Chen L, Wang GL, Zhang YX, Zhou JM, He S, Qin J and Zhu YY: Inhibition of hepatocellular carcinoma growth and angiogenesis by dual silencing of NET-1 and VEGF. J Mol Histol. 44:433–445. 2013. View Article : Google Scholar : PubMed/NCBI