Repression of Dicer is associated with invasive phenotype and chemoresistance in ovarian cancer

Kuang,Yan; Cai,Jing; Li,Donglin; Han,Qin; Cao,Jin; Wang,Zehua

doi:10.3892/ol.2013.1158

Repression of Dicer is associated with invasive phenotype and chemoresistance in ovarian cancer

Authors:
- Yan Kuang
- Jing Cai
- Donglin Li
- Qin Han
- Jin Cao
- Zehua Wang
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Affiliations: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, P.R. China
Published online on: January 28, 2013 https://doi.org/10.3892/ol.2013.1158
Pages: 1149-1154

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Abstract

Dicer is a key enzyme that processes microRNA (miRNA) precursors into their mature form, enabling them to regulate gene expression. However, the effects of Dicer on the biological behavior of cancer cells remain largely unclear. In this study, it was demonstrated that Dicer downregulation promoted cell proliferation, migration and cell cycle progression in A2780 and SKOV3 ovarian cancer cells. Furthermore, Dicer expression was significantly decreased in cisplatin‑resistant A2780 cells (A2780/DDP) compared with parental A2780 cells. Knockdown of Dicer by RNA interference decreased the sensitivity of A2780 cells to cisplatin. Moreover, EZH2 depletion by short hairpin RNA (shRNA)increased the expression of Dicer in vitro. Our data suggest that Dicer is involved in numerous biological/pathological processes, including drug resistance in ovarian cancer, and that its expression may be regulated by EZH2.

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1	Wahid F, Shehzad A, Khan T, et al: Micrornas: Synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta. 1803:1231–1243. 2010. View Article : Google Scholar : PubMed/NCBI
2	Calin GA, Liu CG, Sevignani C, et al: MicroRNA profiling reveals distinct signatures in B cell chronic lymphocytic leukemias. Proc Natl Acad Sci USA. 101:11755–11760. 2004. View Article : Google Scholar : PubMed/NCBI
3	Takamizawa J, Konishi H, Yanagisawa K, et al: Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 64:3753–3756. 2004. View Article : Google Scholar : PubMed/NCBI
4	Michael MZ, O’Connor SM, van Holst Pellekaan NG, et al: Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res. 1:882–891. 2003.PubMed/NCBI
5	Roldo C, Missiaglia E, Hagan JP, et al: MicroRNA expression abnormalities in pancreatic endocrine and acinar tumors are associated with distinctive pathologic features and clinical behavior. J Clin Oncol. 24:4677–4684. 2006. View Article : Google Scholar
6	Bernstein E, Caudy AA, Hammond SM, et al: Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 409:363–366. 2001. View Article : Google Scholar : PubMed/NCBI
7	Kumar MS, Lu J, Mercer KL, et al: Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 39:673–677. 2007. View Article : Google Scholar : PubMed/NCBI
8	Mezzanzanica D, Bagnoli M, De Cecco L, et al: Role of microRNAs in ovarian cancer pathogenesis and potential clinical implications. Int J Biochem Cell Biol. 42:1262–1272. 2010. View Article : Google Scholar : PubMed/NCBI
9	Merritt WM, Lin YG, Han LY, 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
10	Simon JA and Lange CA: Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat Res. 647:21–29. 2008. View Article : Google Scholar : PubMed/NCBI
11	Taniguchi H, Jacinto FV, Villanueva A, et al: Silencing of Kruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer. Oncogene. 31:1988–1994. 2012. View Article : Google Scholar : PubMed/NCBI
12	Fang J, Zhang MX and Li QL: Enhancer of zeste homolog 2 expression is associated with tumor cell proliferation and invasion in cervical cancer. Am J Med Sci. 342:198–204. 2011. View Article : Google Scholar : PubMed/NCBI
13	Guo JF, Cai J, Yu LL, et al: EZH2 regulates expression of p57 and contributes to progression of ovarian cancer in vitro and in vivo. Cancer Science. 102:530–539. 2011. View Article : Google Scholar : PubMed/NCBI
14	Noh H, Hong S, Dong Z, et al: Impaired microRNA processing facilitates breast cancer cell invasion by upregulating urokinase-type plasminogen activator expression. Genes Cancer. 2:140–150. 2011. View Article : Google Scholar : PubMed/NCBI
15	Tang KF, Song GB, Shi YS, et al: Dicer knockdown induces fibronectin-1 expression in HEK293T cells via induction of Egr1. Biochim Biophys Acta. 1800:380–384. 2010. View Article : Google Scholar : PubMed/NCBI
16	Han L, Zhang A, Zhou X, et al: Downregulation of Dicer enhances tumor cell proliferation and invasion. Int J Oncol. 37:299–305. 2010.PubMed/NCBI
17	Kumar MS, Lu J, Mercer KL, et al: Impaired microRNA processing enhances cellular transformation and tumorigenesis. Nat Genet. 39:673–677. 2007. View Article : Google Scholar : PubMed/NCBI
18	McLoughlin HS, Fineberg SK, Ghosh LL, et al: Dicer is required for proliferation, viability, migration and differentiation in corticoneurogenesis. Neuroscience. 223:285–295. 2012. View Article : Google Scholar : PubMed/NCBI
19	Faggad A, Budczies J, Tchernitsa O, 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
20	Bu Y, Lu C, Bian C, et al: Knockdown of Dicer in MCF-7 human breast carcinoma cells results in G1 arrest and increased sensitivity to cisplatin. Oncol Rep. 21:13–17. 2009.PubMed/NCBI
21	Tokumaru S, Suzuki M, Yamada H, et al: Let-7 regulates Dicer expression and constitutes a negative feedback loop. Carcinogenesis. 29:2073–2077. 2008. View Article : Google Scholar : PubMed/NCBI
22	Wiesen JL and Tomasi TB: Dicer is regulated by cellular stresses and interferons. Mol Immunol. 46:1222–1228. 2009. View Article : Google Scholar : PubMed/NCBI
23	Hu S, Yu L, Li Z, Shen Y, et al: Overexpression of EZH2 contributes to acquired cisplatin resistance in ovarian cancer cells in vitro and in vivo. Cancer Biol Ther. 10:788–795. 2010. View Article : Google Scholar : PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−ΔΔ C (T)) Method. Methods. 25:402–408. 2001.