Downregulation of microRNA-17-5p inhibits drug resistance of gastric cancer cells partially through targeting p21

Wang,Ziwei; Ji,Feng

doi:10.3892/ol.2018.7822

Downregulation of microRNA-17-5p inhibits drug resistance of gastric cancer cells partially through targeting p21

Authors:
- Ziwei Wang
- Feng Ji
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Affiliations: Department of Internal Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China, Department of Digestive Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310003, P.R. China
Published online on: January 19, 2018 https://doi.org/10.3892/ol.2018.7822
Pages: 4585-4591

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Abstract

MicroRNAs (miRNAs/miRs) are endogenous small non‑coding RNAs that post‑transcriptionally regulate the expression of genes and serve crucial roles in diverse biological processes. The present study aimed to examine the miRNA expression profile and drug resistance in the SGC7901 cell line and its isogenic drug‑resistant counterpart, SGC7901/cisplatin (DDP) cell line. The potential role of miR‑17‑5p in modulating drug resistance in gastric cancer cells was investigated. Different levels of miRNA expression between SGC7901/DDP and SGC7901 cells were analyzed by miRNA microarray and validated by quantitative polymerase chain reaction. It was indicated that the downregulation of miR‑17‑5p sensitized SGC7901/DDP cells to anticancer drugs. A decreased luciferase activity of p21 3'‑untranslated region‑based reporter in miR‑17‑5p‑transfected SGC7901/DDP cells suggested that p21 may be a direct target gene of miR‑17‑5p. Western blot analysis and flow cytometric assay revealed that the downregulation of miR‑17‑5p increases the sensitivity of SGC7901/DDP cells to DDP‑induced apoptosis. Taken together, these results demonstrated that miR‑17‑5p may perform a role in the development of drug resistance in gastric cancer cells, at least partially by modulating apoptosis via targeting p21.

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1	Du Y, Xu Y, Ding L, Yao H, Yu H, Zhou T and Si J: Down-regulation of miR-141 in gastric cancer and its involvement in cell growth. J Gastroenterol. 44:556–561. 2009. View Article : Google Scholar : PubMed/NCBI
2	Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, et al: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 355:11–20. 2006. View Article : Google Scholar : PubMed/NCBI
3	Fang L, Li H, Wang L, Hu J, Jin T, Wang J and Yang BB: MicroRNA-17-5p promotes chemotherapeutic drug resistance and tumour metastasis of colorectal cancer by repressing PTEN expression. Oncotarget. 5:2974–2987. 2014. View Article : Google Scholar : PubMed/NCBI
4	Rivera F, Vega-Villegas ME and Lόpez-Brea MF: Chemotherapy of advanced gastric cancer. Cancer Treat Rev. 33:315–324. 2007. View Article : Google Scholar : PubMed/NCBI
5	Zhu W, Zhu D, Lu S, Wang T, Wang J, Jiang B, Shu Y and Liu P: MiR-497 modulates multidrug resistance of human cancer cell lines by targeting BCL2. Med Oncol. 29:384–391. 2012. View Article : Google Scholar : PubMed/NCBI
6	Sorrentino A, Liu CG, Addario A, Peschle C, Scambia G and Ferlini C: Role of microRNA in drug-resistant ovarian cancer cells. Gynecol Oncol. 111:478–486. 2008. View Article : Google Scholar : PubMed/NCBI
7	Kovalchuk O, Filkowski J, Meservy J, Ilnytskyy Y, Tryndyak VP, Chekhun VF and Pogribny IP: Involvement of microRNA-451 in resistance of the MCF-7 breast cancer cells to chemotherapeutic drug doxorubicin. Mol Cancer Ther. 7:2152–2159. 2008. View Article : Google Scholar : PubMed/NCBI
8	Hu H, Li S, Cui X, Lv X, Jiao Y, Yu F, Yao H, Song E, Chen Y, Wang M and Lin L: The overexpression of hypomethylated miR-663 induces chemotherapy resistance in human breast cancer cells by targeting heparin sulfate proteoglycan 2 (HSPG2). J Biol Chem. 288:10973–10985. 2013. View Article : Google Scholar : PubMed/NCBI
9	Luo HC: MiRNAs expression profiling of gastric carcinoma and function of significantly down-regulated miR-9 and miR-433. Chongqing Chongqing Med Univ. 1–85. 2010.
10	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
11	Fojo T: Multiple paths to a drug resistance phenotype: Mutations, translocations, deletions and amplification of coding genes or promoter regions, epigenetic changes and microRNA. Drug Resist Updat. 10:59–67. 2007. View Article : Google Scholar : PubMed/NCBI
12	Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, Hong L, Liu J and Fan D: MiR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer. 123:372–379. 2008. View Article : Google Scholar : PubMed/NCBI
13	Kastl L, Brown I and Schofield AC: MiRNAs-34a is associated with docetaxel resistance in human breast cancer cells. Breast Cancer Res Treat. 131:445–454. 2012. View Article : Google Scholar : PubMed/NCBI
14	Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, Alder H, Liu CG, Oue N, Yasui W, et al: Relation between microRNA expression and progression and prognosis of gastric cancer: A microRNA expression analysis. Lancet Oncol. 11:136–146. 2010. View Article : Google Scholar : PubMed/NCBI
15	Szakács G, Paterson JK, Ludwig JA, Booth-genthe C and Gottesman MM: Targeting multidrug resistance in cancer. Nat Rev Drug Discov. 5:219–234. 2006. View Article : Google Scholar : PubMed/NCBI
16	He L, Thomson JM, Hemann MT, Hernando-monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ and Hammond SM: A microRNA polycistron as a potential human oncogene. Nature. 435:828–833. 2005. View Article : Google Scholar : PubMed/NCBI
17	Motoyama K, Inoue H, Takatsuno Y, Tanaka F, Mimori K, Uetake H, Sugihara K and Mori M: Over- and under-expressed microRNAs in human colorectal cancer. Int J Oncol. 34:1069–1075. 2009.PubMed/NCBI
18	Schetter AJ, Leung SY, Sohn JJ, Zanetti KA, Bowman ED, Yanaihara N, Yuen ST, Chan TL, Kwong DL, Au GK, et al: MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA. 299:425–436. 2008. View Article : Google Scholar : PubMed/NCBI
19	Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, Visone R, Iorio M, Roldo C, Ferracin M, et al: A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA. 103:pp. 2257–2261. 2006; View Article : Google Scholar : PubMed/NCBI
20	Li X, Zhang Y, Zhang Y, Ding J, Wu K and Fan D: Survival prediction of gastric cancer by a seven-microRNA signature. Gut. 59:579–585. 2010. View Article : Google Scholar : PubMed/NCBI
21	Dews M, Fox JL, Hultine S, Sundaram P, Wang W, Liu YY, Furth E, Enders GH, El-Deiry W, Schelter JM, et al: The myc-miR-17~92 axis blunts TGF{beta} signaling and production of multiple TGF{beta}-dependent antiangiogenic factors. Cancer Res. 70:8233–8246. 2010. View Article : Google Scholar : PubMed/NCBI
22	Wu Q, Luo G, Yang Z, Zhu F, An Y, Shi Y and Fan D: miR-17-5p promotes proliferation by targeting SOCS6 in gastric cancer cells. FEBS Lett. 588:2055–2062. 2014. View Article : Google Scholar : PubMed/NCBI
23	Fontana L, Fiori ME, Albini S, Cifaldi L, Giovinazzi S, Forloni M, Boldrini R, Donfrancesco A, Federici V, Giacomini P, et al: Antagomir-17-5p abolishes the growth of therapy-resistant neuroblastoma through p21 and BIM. PLoS One. 3:e22362008. View Article : Google Scholar : PubMed/NCBI
24	Yan HL, Xue G, Mei Q, Wang YZ, Ding FX, Liu MF, Lu MH, Tang Y, Yu HY and Sun SH: Repression of the miR-17-92 cluster by p53 has an important function in hypoxia-induced apoptosis. EMBO J. 28:2719–2732. 2009. View Article : Google Scholar : PubMed/NCBI
25	Shen Y, Lu L, Xu J, Meng W, Qing Y, Liu Y, Zhang B and Hu H: Bortezomib induces apoptosis of endometrial cancer cells through microRNA-17-5p by targeting p21. Cell Biol Int. 37:1114–1121. 2013. View Article : Google Scholar : PubMed/NCBI
26	Huether A, Höpfner M, Baradari V, Schuppan D and Scherübl H: EGFR blockade by cetuximab alone or as combination therapy for growth control of hepatocellular cancer. Biochem Pharmacol. 70:1568–1578. 2005. View Article : Google Scholar : PubMed/NCBI
27	Fan M, Sethuraman A, Brown M, Sun W and Pfeffer LM: Systematic analysis of metastasis-associated genes identifies miR-17-5p as a metastatic suppressor of basal-like breast cancer. Breast Cancer Res Treat. 146:487–502. 2014. View Article : Google Scholar : PubMed/NCBI
28	Chatterjee A, Chattopadhyay D and Chakrabarti G: miR-17-5p downregulation contributes to paclitaxel resistance of lung cancer cells through altering beclin1 expression. PLoS One. 9:e957162014. View Article : Google Scholar : PubMed/NCBI