Upregulation of microRNA-34a enhances the DDP sensitivity of gastric cancer cells by modulating proliferation and apoptosis via targeting MET

Zhang,Zhandong; Kong,Ye; Yang,Wei; Ma,Fei; Zhang,Yonglei; Ji,Sheqing; Ma,Er-Min; Liu,Hongxing; Chen,Yongshun; Hua,Yawei

doi:10.3892/or.2016.5016

Upregulation of microRNA-34a enhances the DDP sensitivity of gastric cancer cells by modulating proliferation and apoptosis via targeting MET

Authors:
- Zhandong Zhang
- Ye Kong
- Wei Yang
- Fei Ma
- Yonglei Zhang
- Sheqing Ji
- Er-Min Ma
- Hongxing Liu
- Yongshun Chen
- Yawei Hua
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Affiliations: Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China, Surgical Oncology, The People Hospital of Zhengzhou, Zhengzhou, Henan 450000, P.R. China, Department of Radiotherapy, Affiliated Tumor Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China
Published online on: August 11, 2016 https://doi.org/10.3892/or.2016.5016
Pages: 2391-2397

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Abstract

Cisplatin (DDP) based chemotherapy is still the main strategy of human gastric cancer (GC) treatment. However, drug resistance is a major obstacle for DDP chemotherapy. Recent studies indicated that the resistance could be modulated by the regulation of dysregulated microRNAs (miRs). Previous study also found miR-34a was associated with cell proliferation and apoptosis in human GC; however, the relationship between miR-34a and DDP resistance still remains unexplored. The purpose of this study was to investigate whether miR-34a is associated with DDP resistance in human GC cells. Our study found that the expression of miR-34a was significantly decreased in DDP resistance human GC tissues and DDP resistance human GC SGC7901/DDP cells compared with normal GC tissues and cells. Upregulation of miR-34a enhanced the DDP sensitivity of SGC7901/DDP cells to DDP through the inhibition of cell proliferation and induction of cell apoptosis; on the other hand downregulation of miR-34a could weaken the DDP sensitivity of SGC7901 cells to DDP. Further study found that MET was a direct target of miR-34a and the regulation of MET could affect the DDP sensitivity of SGC7901/DDP cells. Moreover, our study also indicated that upregulation of miR-34a could decrease the expression of MET in SGC7901/DDP cells. Therefore, our findings suggested miR-34a could modulate human gastric cancer cell DDP sensitivity by regulation of cell proliferation and apoptosis via targeting MET, potentially benefiting human GC treatment in the future.

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1	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar
2	Roder DM: The epidemiology of gastric cancer. Gastric Cancer. 5(Suppl 1): 5–11. 2002. View Article : Google Scholar
3	Gallo A and Cha C: Updates on esophageal and gastric cancers. World J Gastroenterol. 12:3237–3242. 2006. View Article : Google Scholar : PubMed/NCBI
4	Gunderson LL: Gastric cancer - patterns of relapse after surgical resection. Semin Radiat Oncol. 12:150–161. 2002. View Article : Google Scholar : PubMed/NCBI
5	Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, et al MAGIC Trial Participants: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 355:11–20. 2006. View Article : Google Scholar : PubMed/NCBI
6	Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, et al CLASSIC trial investigators: Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): A phase 3 open-label, randomised controlled trial. Lancet. 379:315–321. 2012. View Article : Google Scholar : PubMed/NCBI
7	Mesner PW Jr, Budihardjo II and Kaufmann SH: Chemotherapy-induced apoptosis. Adv Pharmacol. 41:461–499. 1997. View Article : Google Scholar : PubMed/NCBI
8	Kaufmann SH and Earnshaw WC: Induction of apoptosis by cancer chemotherapy. Exp Cell Res. 256:42–49. 2000. View Article : Google Scholar : PubMed/NCBI
9	Hannun YA: Apoptosis and the dilemma of cancer chemotherapy. Blood. 89:1845–1853. 1997.PubMed/NCBI
10	Kostova I: Platinum complexes as anticancer agents. Recent Patents Anticancer Drug Discov. 1:1–22. 2006. View Article : Google Scholar
11	Holohan C, Van Schaeybroeck S, Longley DB and Johnston PG: Cancer drug resistance: An evolving paradigm. Nat Rev Cancer. 13:714–726. 2013. View Article : Google Scholar : PubMed/NCBI
12	Longley DB and Johnston PG: Molecular mechanisms of drug resistance. J Pathol. 205:275–292. 2005. View Article : Google Scholar : PubMed/NCBI
13	Nakagawa Y, Sedukhina AS, Okamoto N, Nagasawa S, Suzuki N, Ohta T, Hattori H, Roche-Molina M, Narváez AJ, Jeyasekharan AD, et al: NF-κB signaling mediates acquired resistance after PARP inhibition. Oncotarget. 6:3825–3839. 2015. View Article : Google Scholar : PubMed/NCBI
14	Halilovic E, She QB, Ye Q, Pagliarini R, Sellers WR, Solit DB and Rosen N: PIK3CA mutation uncouples tumor growth and cyclin D1 regulation from MEK/ERK and mutant KRAS signaling. Cancer Res. 70:6804–6814. 2010. View Article : Google Scholar : PubMed/NCBI
15	Michaelis M, Rothweiler F, Barth S, Cinatl J, van Rikxoort M, Löschmann N, Voges Y, Breitling R, von Deimling A, Rödel F, et al: Adaptation of cancer cells from different entities to the MDM2 inhibitor nutlin-3 results in the emergence of p53-mutated multi-drug-resistant cancer cells. Cell Death Dis. 2:e2432011. View Article : Google Scholar : PubMed/NCBI
16	Lin X, Zhang X, Wang Q, Li J, Zhang P, Zhao M and Li X: Perifosine downregulates MDR1 gene expression and reverses multidrug-resistant phenotype by inhibiting PI3K/Akt/NF-κB signaling pathway in a human breast cancer cell line. Neoplasma. 59:248–256. 2012. View Article : Google Scholar
17	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
18	Bartel DP: MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI
19	Ma L, Teruya-Feldstein J and Weinberg RA: Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 449:682–688. 2007. View Article : Google Scholar : PubMed/NCBI
20	Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson EG, Teruya-Feldstein J, Bell GW and Weinberg RA: Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol. 28:341–347. 2010. View Article : Google Scholar : PubMed/NCBI
21	Cho WC: MicroRNAs: Potential biomarkers for cancer diagnosis, prognosis and targets for therapy. Int J Biochem Cell Biol. 42:1273–1281. 2010. View Article : Google Scholar
22	Cho WC: MicroRNAs in cancer - from research to therapy. Biochim Biophys Acta. 1805:209–217. 2010.
23	Gabriely G, Teplyuk NM and Krichevsky AM: Context effect: microRNA-10b in cancer cell proliferation, spread and death. Autophagy. 7:1384–1386. 2011. View Article : Google Scholar : PubMed/NCBI
24	Xiang Y, Ma N, Wang D, Zhang Y, Zhou J, Wu G, Zhao R, Huang H, Wang X, Qiao Y, et al: MiR-152 and miR-185 co-contribute to ovarian cancer cells cisplatin sensitivity by targeting DNMT1 directly: A novel epigenetic therapy independent of decitabine. Oncogene. 33:378–386. 2014. View Article : Google Scholar
25	Shang Y, Zhang Z, Liu Z, Feng B, Ren G, Li K, Zhou L, Sun Y, Li M, Zhou J, et al: miR-508-5p regulates multidrug resistance of gastric cancer by targeting ABCB1 and ZNRD1. Oncogene. 33:3267–3276. 2014. View Article : Google Scholar
26	Sui C, Meng F, Li Y and Jiang Y: miR-148b reverses cisplatin-resistance in non-small cell cancer cells via negatively regulating DNA (cytosine-5)-methyltransferase 1(DNMT1) expression. J Transl Med. 13:1322015. View Article : Google Scholar : PubMed/NCBI
27	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
28	Yu ZW, Zhong LP, Ji T, Zhang P, Chen WT and Zhang CP: MicroRNAs contribute to the chemoresistance of cisplatin in tongue squamous cell carcinoma lines. Oral Oncol. 46:317–322. 2010. View Article : Google Scholar : PubMed/NCBI
29	Sorrentino A, Liu CG, Addario A, Peschle C, Scambia G and Ferlini C: Role of microRNAs in drug-resistant ovarian cancer cells. Gynecol Oncol. 111:478–486. 2008. View Article : Google Scholar : PubMed/NCBI
30	Wei B, Huang QY, Huang SR, Mai W and Zhong XG: MicroRNA-34a attenuates the proliferation, invasion and metastasis of gastric cancer cells via downregulation of MET. Mol Med Rep. 12:5255–5261. 2015.PubMed/NCBI
31	Du Y, Zhu M, Zhou X, Huang Z, Zhu J, Xu J, Cheng G, Shu Y, Liu P, Zhu W, et al: miR-20a enhances cisplatin resistance of human gastric cancer cell line by targeting NFKBIB. Tumour Biol. 37:1261–1269. 2016. View Article : Google Scholar
32	Yao Y, Suo AL, Li ZF, Liu LY, Tian T, Ni L, Zhang WG, Nan KJ, Song TS and Huang C: MicroRNA profiling of human gastric cancer. Mol Med Rep. 2:963–970. 2009.PubMed/NCBI
33	Wong MY, Yu Y, Walsh WR and Yang JL: microRNA-34 family and treatment of cancers with mutant or wild-type p53 (Review). Int J Oncol. 38:1189–1195. 2011.PubMed/NCBI
34	Kumar B, Yadav A, Lang J, Teknos TN and Kumar P: Dysregulation of microRNA-34a expression in head and neck squamous cell carcinoma promotes tumor growth and tumor angiogenesis. PLoS One. 7:e376012012. View Article : Google Scholar : PubMed/NCBI
35	Shen Z, Zhan G, Ye D, Ren Y, Cheng L, Wu Z and Guo J: MicroRNA-34a affects the occurrence of laryngeal squamous cell carcinoma by targeting the antiapoptotic gene survivin. Med Oncol. 29:2473–2480. 2012. View Article : Google Scholar : PubMed/NCBI
36	Li Y, Guessous F, Zhang Y, Dipierro C, Kefas B, Johnson E, Marcinkiewicz L, Jiang J, Yang Y, Schmittgen TD, et al: MicroRNA-34a inhibits glioblastoma growth by targeting multiple oncogenes. Cancer Res. 69:7569–7576. 2009. View Article : Google Scholar : PubMed/NCBI
37	Cho WC: OncomiRs: The discovery and progress of microRNAs in cancers. Mol Cancer. 6:602007. View Article : Google Scholar : PubMed/NCBI
38	Lutterbach B, Zeng Q, Davis LJ, Hatch H, Hang G, Kohl NE, Gibbs JB and Pan BS: Lung cancer cell lines harboring MET gene amplification are dependent on Met for growth and survival. Cancer Res. 67:2081–2088. 2007. View Article : Google Scholar : PubMed/NCBI
39	Takeuchi H, Bilchik A, Saha S, Turner R, Wiese D, Tanaka M, Kuo C, Wang HJ and Hoon DS: c-MET expression level in primary colon cancer: A predictor of tumor invasion and lymph node metastases. Clin Cancer Res. 9:1480–1488. 2003.PubMed/NCBI
40	Sawada K, Radjabi AR, Shinomiya N, Kistner E, Kenny H, Becker AR, Turkyilmaz MA, Salgia R, Yamada SD, Vande Woude GF, et al: c-Met overexpression is a prognostic factor in ovarian cancer and an effective target for inhibition of peritoneal dissemination and invasion. Cancer Res. 67:1670–1679. 2007. View Article : Google Scholar : PubMed/NCBI
41	Dang Y, Luo D, Rong M and Chen G: Underexpression of miR-34a in hepatocellular carcinoma and its contribution towards enhancement of proliferating inhibitory effects of agents targeting c-MET. PLoS One. 8:e610542013. View Article : Google Scholar : PubMed/NCBI