Dicer affects cisplatin‑mediated apoptosis in epithelial ovarian cancer cells

Wang,Xi; Chen,Hui; Wen,Yiping; Yang,Xiaoxin; Han,Qing; Jiang,Ping; Huang,Zaiju; Cai,Jing; Wang,Zehua

doi:10.3892/mmr.2018.9452

Dicer affects cisplatin‑mediated apoptosis in epithelial ovarian cancer cells

Authors:
- Xi Wang
- Hui Chen
- Yiping Wen
- Xiaoxin Yang
- Qing Han
- Ping Jiang
- Zaiju Huang
- Jing Cai
- Zehua Wang
View Affiliations

Affiliations: Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Obstetrics and Gynecology, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan, Hubei 430022, P.R. China, University Clinic for Medical Radiation Physics, Medical Campus Pius‑Hospital, Carl von Ossietzky University, Oldenburg D‑26121, Germany
Published online on: September 4, 2018 https://doi.org/10.3892/mmr.2018.9452
Pages: 4381-4387
Copyright: © Wang 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 an essential enzyme that processes micro (mi)-RNA precursors into mature miRNAs, and serves a critical role in cancer development and progression by regulating gene expression. However, the role of Dicer in cisplatin‑mediated apoptosis and chemotherapy resistance in epithelial ovarian cancer (EOC) cells is poorly understood. In the present study, Dicer was expressed at low levels in cisplatin‑resistant A2780 cells when compared with parental cells. In addition, knocking down Dicer using short hairpin RNA decreased the sensitivity of A2780 and CAOV3 cells to cisplatin. Furthermore, downregulating Dicer significantly inhibited cisplatin‑induced apoptosis in ovarian cancer cells, and decreased the levels of proteins involved in apoptosis signaling pathways, including P73, P63, P53, caspase‑9 and caspase‑3. These findings indicated that Dicer may be a promising target for overcoming drug resistance in ovarian cancer.

View Figures

View References

1	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
2	Jayson GC, Kohn EC, Kitchener HC and Ledermann JA: Ovarian cancer. Lancet. 384:1376–1388. 2014. View Article : Google Scholar : PubMed/NCBI
3	Bernstein E, Caudy AA, Hammond SM and Hannon GJ: Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 409:363–366. 2001. View Article : Google Scholar : PubMed/NCBI
4	Krol J, Loedige I and Filipowicz W: The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 11:597–610. 2010. View Article : Google Scholar : PubMed/NCBI
5	Bahubeshi A, Tischkowitz M and Foulkes WD: miRNA processing and human cancer: DICER1 cuts the mustard. Sci Transl Med. 3:111ps462011. View Article : Google Scholar : PubMed/NCBI
6	Chen X, Li WF, Wu X, Zhang HC, Chen L, Zhang PY, Liu LY, Ma D, Chen T, Zhou L, et al: Dicer regulates non-homologous end joining and is associated with chemosensitivity in colon cancer patients. Carcinogenesis. 38:873–882. 2017. View Article : Google Scholar : PubMed/NCBI
7	Sha LY, Zhang Y, Wang W, Sui X, Liu SK, Wang T and Zhang H: MiR-18a upregulation decreases Dicer expression and confers paclitaxel resistance in triple negative breast cancer. Eur Rev Med Pharmacol Sci. 20:2201–2208. 2016.PubMed/NCBI
8	Chen JC, Su YH, Chiu CF, Chang YW, Yu YH, Tseng CF, Chen HA and Su JL: Suppression of Dicer increases sensitivity to gefitinib in human lung cancer cells. Ann Surg Oncol. 21 Suppl 4:S555–S563. 2014. View Article : Google Scholar : PubMed/NCBI
9	Zhu Y, Cai L, Guo J, Chen N, Yi X, Zhao Y, Cai J and Wang Z: Depletion of Dicer promotes epithelial ovarian cancer progression by elevating PDIA3 expression. Tumour Biol. 37:14009–14023. 2016. View Article : Google Scholar : PubMed/NCBI
10	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
11	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. View Article : Google Scholar : PubMed/NCBI
12	Hu S, Yu L, Li Z, Shen Y, Wang J, Cai J, Xiao L and Wang Z: 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
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Holzer AK and Howell SB: The internalization and degradation of human copper transporter 1 following cisplatin exposure. Cancer Res. 66:10944–10952. 2006. View Article : Google Scholar : PubMed/NCBI
15	Ahsan A, Hiniker SM, Ramanand SG, Nyati S, Hegde A, Helman A, Menawat R, Bhojani MS, Lawrence TS and Nyati MK: Role of epidermal growth factor receptor degradation in cisplatin-induced cytotoxicity in head and neck cancer. Cancer Res. 70:2862–2869. 2010. View Article : Google Scholar : PubMed/NCBI
16	Cai L, Wang Z and Liu D: Interference with endogenous EZH2 reverses the chemotherapy drug resistance in cervical cancer cells partly by up-regulating Dicer expression. Tumour Biol. 37:6359–6369. 2016. View Article : Google Scholar : PubMed/NCBI
17	Kawahara K, Nakayama H, Nagata M, Yoshida R, Hirosue A, Tanaka T, Nakagawa Y, Matsuoka Y, Kojima T, Takamune Y, et al: A low Dicer expression is associated with resistance to 5-FU-based chemoradiotherapy and a shorter overall survival in patients with oral squamous cell carcinoma. J Oral Pathol Med. 43:350–356. 2014. View Article : Google Scholar : PubMed/NCBI
18	Bu Y, Lu C, Bian C, Wang J, Li J, Zhang B, Li Z, Brewer G and Zhao RC: 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
19	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
20	Swahari V, Nakamura A, Baran-Gale J, Garcia I, Crowther AJ, Sons R, Gershon TR, Hammond S, Sethupathy P and Deshmukh M: Essential function of dicer in resolving DNA damage in the rapidly dividing cells of the developing and malignant cerebellum. Cell Rep. 14:216–224. 2016. View Article : Google Scholar : PubMed/NCBI
21	Aubrey BJ, Kelly GL, Janic A, Herold MJ and Strasser A: How does p53 induce apoptosis and how does this relate to p53-mediated tumour suppression? Cell Death Differ. 25:104–113. 2018. View Article : Google Scholar : PubMed/NCBI
22	Mollereau B and Ma D: The p53 control of apoptosis and proliferation: Lessons from Drosophila. Apoptosis. 19:1421–1429. 2014. View Article : Google Scholar : PubMed/NCBI
23	Gonzalez VM, Fuertes MA, Alonso C and Perez JM: Is cisplatin-induced cell death always produced by apoptosis? Mol Pharmacol. 59:657–663. 2001. View Article : Google Scholar : PubMed/NCBI
24	Domcke S, Sinha R, Levine DA, Sander C and Schultz N: Evaluating cell lines as tumour models by comparison of genomic profiles. Nat Commun. 4:21262013. View Article : Google Scholar : PubMed/NCBI
25	Tran TQ, Lowman XH, Reid MA, Mendez-Dorantes C, Pan M, Yang Y and Kong M: Tumor-associated mutant p53 promotes cancer cell survival upon glutamine deprivation through p21 induction. Oncogene. 36:1991–2001. 2017. View Article : Google Scholar : PubMed/NCBI
26	Lu C, Xie Z and Peng Q: MiRNA-107 enhances chemosensitivity to paclitaxel by targeting antiapoptotic factor Bcl-w in non small cell lung cancer. Am J Cancer Res. 7:1863–1873. 2017.PubMed/NCBI
27	Wu G, Wang J, Chen G and Zhao X: microRNA-204 modulates chemosensitivity and apoptosis of prostate cancer cells by targeting zinc-finger E-box-binding homeobox 1 (ZEB1). Am J Transl Res. 9:3599–3610. 2017.PubMed/NCBI