MicroRNA-149 suppresses the proliferation and increases the sensitivity of ovarian cancer cells to cisplatin by targeting X-linked inhibitor of apoptosis

Sun,Lin; Zhai,Ruixia; Zhang,Li; Zhao,Shuping

doi:10.3892/ol.2018.8240

MicroRNA-149 suppresses the proliferation and increases the sensitivity of ovarian cancer cells to cisplatin by targeting X-linked inhibitor of apoptosis

Authors:
- Lin Sun
- Ruixia Zhai
- Li Zhang
- Shuping Zhao
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Affiliations: Department of Gynecology, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, P.R. China, Department of Obstetrics, Affiliated Hospital of Jining Medical University, Jining, Shandong 272100, P.R. China, Department of Gynecology, Affiliated Hospital of Jining Medical University, Jining, Shandong 272100, P.R. China, Department of Gynecology, Qingdao Women and Children's Hospital of Qingdao University, Qingdao, Shandong 266034, P.R. China
Published online on: March 12, 2018 https://doi.org/10.3892/ol.2018.8240
Pages: 7328-7334

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Abstract

Currently, ovarian cancer is identified as one of the leading causes of cancer‑associated mortality in females. Despite numerous efforts that were made on developing novel treatments for ovarian cancer, the survival rate remains unsatisfactory. Considering the important regulatory role of miRNAs in different types of cancer, the present study aims to identify a novel therapeutic target for treatment of ovarian cancer. The expression of miR‑149 was detected using reverse transcription‑quantitative polymerase chain reaction in cancerous and normal cells. Furthermore, the effects of miR‑149 on ovarian cancer cell activities were investigated using MTT assay, colony formation, flow cytometry and western blotting analysis. In the present study, it was revealed that microRNA (miR)‑149 was significantly downregulated in ovarian cancer tissues and cell lines, and that the miR‑149 expression was correlated with the patient prognosis. In addition, it was observed that forced expression of miR‑149 increased the sensitivity of ovarian cancer cell to cisplatin. Based on bioinformatics analysis and luciferase assay, X‑linked inhibitor of apoptosis (XIAP) was identified as a direct target gene of miR‑149 in ovarian cancer cells. It was also demonstrated that XIAP expression was upregulated in the ovarian cancer tissues and cell lines, while it was negatively correlated with miR‑149 in these tissues and cells. Furthermore, results revealed that ectopic expression of XIAP was able to abolish the miR‑149‑enhanced cell sensitivity to cisplatin. In conclusion, the present study revealed that miR‑149 functioned as a tumor suppressor in the progression of ovarian cancer, increasing the sensitivity of ovarian cancer cells to cisplatin treatment.

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1	Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin. 65:87–108. 2015. View Article : Google Scholar : PubMed/NCBI
2	Tian S, Zhang M, Chen X, Liu Y and Lou G: MicroRNA-595 sensitizes ovarian cancer cells to cisplatin by targeting ABCB1. Oncotarget. 7:87091–87099. 2016. View Article : Google Scholar : PubMed/NCBI
3	Flavin R, Smyth P, Barrett C, Russell S, Wen H, Wei J, Laios A, O'Toole S, Ring M, Denning K, et al: miR-29b expression is associated with disease-free survival in patients with ovarian serous carcinoma. Int J Gynecol Cancer. 19:641–647. 2009. View Article : Google Scholar : PubMed/NCBI
4	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
5	Miao Y, Zhang LF, Guo R, Liang S, Zhang M, Shi S, Shang-Guan CF, Liu MF and Li B: (18)F-FDG PET/CT for monitoring the response of breast cancer to miR-143-based therapeutics by targeting tumor glycolysis. Mol Ther Nucleic Acids. 5:e3572016. View Article : Google Scholar : PubMed/NCBI
6	Cai M, Wang Z, Zhang J, Zhou H, Jin L, Bai R and Weng Y: Adam17, a Target of Mir-326, Promotes Emt-Induced Cells Invasion in Lung Adenocarcinoma. Cell Physiol Biochem. 36:1175–1185. 2015. View Article : Google Scholar : PubMed/NCBI
7	Perry MM, Baker JE, Gibeon DS, Adcock IM and Chung KF: Airway smooth muscle hyperproliferation is regulated by microRNA-221 in severe asthma. Am J Respir Cell Mol Biol. 50:7–17. 2014.PubMed/NCBI
8	O'Leary L, Sevinc K, Papazoglou IM, Tildy B, Detillieux K, Halayko AJ, Chung KF and Perry MM: Airway smooth muscle inflammation is regulated by microRNA-145 in COPD. FEBS Lett. 590:1324–1334. 2016. View Article : Google Scholar : PubMed/NCBI
9	Baldwin S, Deighan C, Bandeira E, Kwak KJ, Rahman M, Nana-Sinkam P, Lee LJ and Paulaitis ME: Analyzing the miRNA content of extracellular vesicles by fluorescence nanoparticle tracking. Nanomedicine. 13:765–770. 2017. View Article : Google Scholar : PubMed/NCBI
10	Goeppert B, Ernst C, Baer C, Roessler S, Renner M, Mehrabi A, Hafezi M, Pathil A, Warth A, Stenzinger A, et al: Cadherin-6 is a putative tumor suppressor and target of epigenetically dysregulated miR-429 in cholangiocarcinoma. Epigenetics. 11:780–790. 2016. View Article : Google Scholar : PubMed/NCBI
11	Xi S, Inchauste S, Guo H, Shan J, Xiao Z, Xu H, Miettenen M, Zhang MR, Hong JA, Raiji MT, et al: Cigarette smoke mediates epigenetic repression of miR-217 during esophageal adenocarcinogenesis. Oncogene. 34:5548–5559. 2015. View Article : Google Scholar : PubMed/NCBI
12	Chen Y, Zhao J, Luo Y, Wang Y and Jiang Y: Downregulated expression of miRNA-149 promotes apoptosis in side population cells sorted from the TSU prostate cancer cell line. Oncol Rep. 36:2587–2600. 2016. View Article : Google Scholar : PubMed/NCBI
13	Cao D, Jia Z, You L, Wu Y, Hou Z, Suo Y, Zhang H, Wen S, Tsukamoto T, Oshima M, et al: 18β-glycyrrhetinic acid suppresses gastric cancer by activation of miR-149-3p-Wnt-1 signaling. Oncotarget. 7:71960–71973. 2016. View Article : Google Scholar : PubMed/NCBI
14	Assem H, Rambau PF, Lee S, Ogilvie T, Sienko A, Kelemen LE and Köbel M: High-grade endometrioid carcinoma of the ovary: A clinicopathologic study of 30 cases. Am J Surg Pathol. Jan 5–2018.(Epub ahead of print). View Article : Google Scholar : PubMed/NCBI
15	Guenther LM, Rowe RG, Acharya PT, Swenson DW, Meyer SC, Clinton CM, Guo D, Sridharan M, London WB, Grier HE, et al: Response evaluation criteria in solid tumors (RECIST) following neoadjuvant chemotherapy in osteosarcoma. Pediatr Blood Cancer. Dec 18–2017.(Epub ahead of print). PubMed/NCBI
16	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
17	Wang H, Sun M, Guo J, Ma L, Jiang H, Gu L, Wen H, Liao S, Chen J, Zeng B, et al: 3-O-(Z)-coumaroyloleanolic acid overcomes Cks1b-induced chemoresistance in lung cancer by inhibiting Hsp90 and MEK pathways. Biochem Pharmacol. 135:35–49. 2017. View Article : Google Scholar : PubMed/NCBI
18	Pan CW, Jin X, Zhao Y, Pan Y, Yang J, Karnes RJ, Zhang J, Wang L and Huang H: AKT-phosphorylated FOXO1 suppresses ERK activation and chemoresistance by disrupting IQGAP1-MAPK interaction. EMBO J. 36:995–1010. 2017. View Article : Google Scholar : PubMed/NCBI
19	Ma H, Yokoyama S, Saiki I and Hayakawa Y: Chemosensitizing effect of saikosaponin B on B16F10 melanoma cells. Nutr Cancer. 69:505–511. 2017. View Article : Google Scholar : PubMed/NCBI
20	D'Angelo D, Mussnich P, Arra C, Battista S and Fusco A: Critical role of HMGA proteins in cancer cell chemoresistance. J Mol Med (Berl). 95:353–360. 2017. View Article : Google Scholar : PubMed/NCBI
21	Chen S, Huang J, Liu Z, Liang Q, Zhang N and Jin Y: FAM83A is amplified and promotes cancer stem cell-like traits and chemoresistance in pancreatic cancer. Oncogenesis. 6:e3002017. View Article : Google Scholar : PubMed/NCBI
22	Pu Y, Zhao F, Wang H and Cai S: MiR-34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene. Sci Rep. 7:442182017. View Article : Google Scholar : PubMed/NCBI
23	Liu Y, Zhang B, Shi T and Qin H: miR-182 promotes tumor growth and increases chemoresistance of human anaplastic thyroid cancer by targeting tripartite motif 8. Onco Targets Ther. 10:1115–1122. 2017. View Article : Google Scholar : PubMed/NCBI
24	Jin L, Li Y, Liu J, Yang S, Gui Y, Mao X, Nie G and Lai Y: Tumor suppressor miR-149-5p is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma. Mol Med Rep. 13:5386–5392. 2016. View Article : Google Scholar : PubMed/NCBI
25	Fan SJ, Li HB, Cui G, Kong XL, Sun LL, Zhao YQ, Li YH and Zhou J: miRNA-149* promotes cell proliferation and suppresses apoptosis by mediating JunB in T-cell acute lymphoblastic leukemia. Leuk Res. 41:62–70. 2016. View Article : Google Scholar : PubMed/NCBI
26	Luo G, Chao YL, Tang B, Li BS, Xiao YF, Xie R, Wang SM, Wu YY, Dong H, Liu XD and Yang SM: miR-149 represses metastasis of hepatocellular carcinoma by targeting actin-regulatory proteins PPM1F. Oncotarget. 6:37808–37823. 2015. View Article : Google Scholar : PubMed/NCBI
27	Riley A, Jordan LE and Holcik M: Distinct 5′ UTRs regulate XIAP expression under normal growth conditions and during cellular stress. Nucleic Acids Res. 38:4665–4674. 2010. View Article : Google Scholar : PubMed/NCBI
28	Deveraux QL, Takahashi R, Salvesen GS and Reed JC: X-linked IAP is a direct inhibitor of cell-death proteases. Nature. 388:300–304. 1997. View Article : Google Scholar : PubMed/NCBI
29	Tamm I, Kornblau SM, Segall H, Krajewski S, Welsh K, Kitada S, Scudiero DA, Tudor G, Qui YH, Monks A, et al: Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 6:1796–1803. 2000.PubMed/NCBI
30	Pardo OE, Lesay A, Arcaro A, Lopes R, Ng BL, Warne PH, McNeish IA, Tetley TD, Lemoine NR, Mehmet H, et al: Fibroblast growth factor 2-mediated translational control of IAPs blocks mitochondrial release of Smac/DIABLO and apoptosis in small cell lung cancer cells. Mol Cell Biol. 23:7600–7610. 2003. View Article : Google Scholar : PubMed/NCBI
31	Ding WB, Wang YX and Dong CW: microRNA15b induced SMCC7721 apoptosis via down-regulation of XIAP. Eur Rev Med Pharmacol Sci. 21:542–548. 2017.PubMed/NCBI
32	Li X, Chen W, Zeng W, Wan C, Duan S and Jiang S: microRNA-137 promotes apoptosis in ovarian cancer cells via the regulation of XIAP. Br J Cancer. 116:66–76. 2017. View Article : Google Scholar : PubMed/NCBI
33	Han J, Liu Z, Wang N and Pan W: MicroRNA-874 inhibits growth, induces apoptosis and reverses chemoresistance in colorectal cancer by targeting X-linked inhibitor of apoptosis protein. Oncol Rep. 36:542–550. 2016. View Article : Google Scholar : PubMed/NCBI
34	Wu Q, Yan H, Tao SQ, Wang XN, Mou L, Chen P, Cheng XW, Wu WY and Wu ZS: XIAP 3′-untranslated region as a ceRNA promotes FSCN1 function in inducing the progression of breast cancer by binding endogenous miR-29a-5p. Oncotarget. 8:16784–16800. 2017.PubMed/NCBI