miR-193b acts as a cisplatin sensitizer via the caspase-3-dependent pathway in HCC chemotherapy

Yin,Wenjun; Nie,Yuehua; Zhang,Zhiwei; Xie,Liming; He,Xiusheng

doi:10.3892/or.2015.3996

miR-193b acts as a cisplatin sensitizer via the caspase-3-dependent pathway in HCC chemotherapy

Authors:
- Wenjun Yin
- Yuehua Nie
- Zhiwei Zhang
- Liming Xie
- Xiusheng He
View Affiliations

Affiliations: Cancer Research Institute of Medical College, University of Southern China, University Key Laboratory of Cancer Cellular and Molecular Pathology in Hunan Province, Hengyang, Hunan 421001, P.R. China, Department of Radiation Oncology, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China, Department of Chemotherapy Oncology, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, P.R. China
Published online on: May 19, 2015 https://doi.org/10.3892/or.2015.3996
Pages: 368-374

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

Mounting evidence suggests that microRNAs (miRNAs) play important roles in the development of cancer by targeting expression of tumor-related genes. In the present study, downregulation of miR-193b was observed in hepatocellular carcinoma (HCC) tissues and HCC cell lines by quantitative RT-PCR analyses, suggesting that miR-193b is a tumor-suppressor in HCC. More importantly, miR-193b significantly enhanced the cytotoxicity of cisplatin in HepG2 cells by targeting Mcl-1. Knockdown of the Mcl-1 gene by specific siRNA exhibited a function similar to miR-193b on sensitizing HepG2 cells to cisplatin-inducing cytotoxicity. Furthermore, the miR-193b-induced sensitization of HepG2 cells to cisplatin cytotoxicity was abolished by the transfection of Mcl-1 expression plasmid that lacked the 3'-untranslated region (3'-UTR). In addition, activation of caspase-3 was needed for sensitization by miR-193b to cisplatin-mediated cell death. Thus, the present study revealed the downregulation of miR-193b in HCC cells and illustrated a synergistic effect on cisplatin-induced apoptosis by targeting Mcl-1.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Nault JC, Calderaro J, Di Tommaso L, Balabaud C, Zafrani ES, Bioulac-Sage P, Roncalli M and Zucman-Rossi J: Telomerase reverse transcriptase promoter mutation is an early somatic genetic alteration in the transformation of premalignant nodules in hepatocellular carcinoma on cirrhosis. Hepatology. 60:1983–1992. 2014. View Article : Google Scholar : PubMed/NCBI
3	Kerr SH and Kerr DJ: Novel treatments for hepatocellular cancer. Cancer Lett. 286:114–120. 2009. View Article : Google Scholar : PubMed/NCBI
4	Arslan C, Ozdemir E, Dogan E, Ozisik Y and Altundag K: Secondary hematological malignancies after treatment of non-metastatic breast cancer. J BUON. 16:744–750. 2011.
5	Roufayel R, Johnston DS and Mosser DD: The elimination of miR-23a in heat-stressed cells promotes NOXA-induced cell death and is prevented by HSP70. Cell Death Dis. 27:e15462014. View Article : Google Scholar
6	Nair N and Gongora E: MicroRNAs as therapeutic targets in cardiomyopathies: Myth or reality? Biomol Concepts. 5:439–448. 2014. View Article : Google Scholar : PubMed/NCBI
7	Zhang H, Cheng Y, Jia C, Yu S, Xiao Y and Chen J: MicroRNA-29s could target AKT2 to inhibit gastric cancer cells invasion ability. Med Oncol. 32:3422015. View Article : Google Scholar
8	Zhang L, Ge Y and Fuchs E: miR-125b can enhance skin tumor initiation and promote malignant progression by repressing differentiation and prolonging cell survival. Genes Dev. 28:2532–2546. 2014. View Article : Google Scholar : PubMed/NCBI
9	Wang S and Li K: MicroRNA-96 regulates RGC-5 cell growth through caspase-dependent apoptosis. Int J Clin Exp Med. 7:3694–3702. 2014.PubMed/NCBI
10	Wolfson B, Eades G and Zhou Q: Roles of microRNA-140 in stem cell-associated early stage breast cancer. World J Stem Cells. 6:591–597. 2014. View Article : Google Scholar : PubMed/NCBI
11	Mo ZH, Wu XD, Li S, Fei BY and Zhang B: Expression and clinical significance of microRNA-376a in colorectal cancer. Asian Pac J Cancer Prev. 15:9523–9527. 2014. View Article : Google Scholar : PubMed/NCBI
12	Woo SM, Min KJ, Seo BR, Nam JO, Choi KS, Yoo YH and Kwon TK: Cafestol overcomes ABT-737 resistance in Mcl-1-overexpressed renal carcinoma Caki cells through downregulation of Mcl-1 expression and upregulation of Bim expression. Cell Death Dis. 5:e15142014. View Article : Google Scholar : PubMed/NCBI
13	Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, Barbisin M, Xu NL, Mahuvakar VR, Andersen MR, et al: Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res. 33:e1792005. View Article : Google Scholar : PubMed/NCBI
14	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
15	Amaral C, Borges M, Melo S, da Silva ET, Correia-da-Silva G and Teixeira N: Apoptosis and autophagy in breast cancer cells following exemestane treatment. PLoS One. 7:e423982012. View Article : Google Scholar : PubMed/NCBI
16	Mu YP, Tang S, Sun WJ, Gao WM, Wang M and Su XL: Association of miR-193b down-regulation and miR-196a up-regulation with clinicopathological features and prognosis in gastric cancer. Asian Pac J Cancer Prev. 15:8893–8900. 2014. View Article : Google Scholar : PubMed/NCBI
17	Li J, Kong F, Wu K, Song K, He J and Sun W: miR-193b directly targets STMN1 and uPA genes and suppresses tumor growth and metastasis in pancreatic cancer. Mol Med Rep. 10:2613–2620. 2014.PubMed/NCBI
18	Liu R, Liu X, Zheng Y, Gu J, Xiong S, Jiang P, Jiang X, Huang E, Yang Y, Ge D, et al: MicroRNA-7 sensitizes non-small cell lung cancer cells to paclitaxel. Oncol Lett. 8:2193–2200. 2014.PubMed/NCBI
19	Boyerinas B, Park SM, Murmann AE, Gwin K, Montag AG, Zillhardt M, Hua YJ, Lengyel E and Peter ME: Let-7 modulates acquired resistance of ovarian cancer to Taxanes via IMP-1-mediated stabilization of multidrug resistance 1. Int J Cancer. 130:1787–1797. 2012. View Article : Google Scholar
20	Koga C, Kobayashi S, Nagano H, Tomimaru Y, Hama N, Wada H, Kawamoto K, Eguchi H, Konno M, Ishii H, et al: Reprogramming using microRNA-302 improves drug sensitivity in hepatocellular carcinoma cells. Ann Surg Oncol. 21(Suppl 4): S591–S600. 2014. View Article : Google Scholar : PubMed/NCBI
21	Creagh EM: Caspase crosstalk: integration of apoptotic and innate immune signalling pathways. Trends Immunol. 35:631–640. 2014. View Article : Google Scholar : PubMed/NCBI
22	Childs BG, Baker DJ, Kirkland JL, Campisi J and van Deursen JM: Senescence and apoptosis: Dueling or complementary cell fates? EMBO Rep. 15:1139–1153. 2014. View Article : Google Scholar : PubMed/NCBI
23	Setia S, Nehru B and Sanyal SN: Celecoxib prevents colitis associated colon carcinogenesis: An upregulation of apoptosis. Pharmacol Rep. 66:1083–1091. 2014. View Article : Google Scholar : PubMed/NCBI
24	Yang P, Tuo L, Wu Q and Cao X: Licochalcone-A sensitizes human esophageal carcinoma cells to TRAIL-mediated apoptosis by proteasomal degradation of XIAP. Hepatogastroenterology. 61:1229–1234. 2014.PubMed/NCBI
25	Lee HG, Lee JM, Shin SJ, Kwon SH, Lee GS, Song CH, Choi ES, Cha SD and Cho CH: Salinomycin inhibited cell proliferation and induced apoptosis in human uterine leiomyoma cells. Obstet Gynecol Sci. 57:501–506. 2014. View Article : Google Scholar : PubMed/NCBI
26	Zhao J, Li X, Zou M, He J, Han Y, Wu D, Yang H and Wu J: miR-135a inhibition protects A549 cells from LPS-induced apoptosis by targeting Bcl-2. Biochem Biophys Res Commun. 452:951–957. 2014. View Article : Google Scholar : PubMed/NCBI
27	Rao YM, Shi HR, Ji M and Chen CH: miR-106a targets Mcl-1 to suppress cisplatin resistance of ovarian cancer A2780 cells. J Huazhong Univ Sci Technolog Med Sci. 33:567–572. 2013. View Article : Google Scholar : PubMed/NCBI
28	Zhang R, Li Y, Dong X, Peng L and Nie X: miR-363 sensitizes cisplatin-induced apoptosis targeting in Mcl-1 in breast cancer. Med Oncol. 31:3472014. View Article : Google Scholar : PubMed/NCBI
29	Geserick P, Wang J, Feoktistova M and Leverkus M: The ratio of Mcl-1 and Noxa determines ABT737 resistance in squamous cell carcinoma of the skin. Cell Death Dis. 5:e14122014. View Article : Google Scholar : PubMed/NCBI