miR‑195‑5p regulates multi‑drug resistance of gastric cancer cells via targeting ZNF139

Nie,Hongfeng; Mu,Jixing; Wang,Jinsheng; Li,Yong

doi:10.3892/or.2018.6524

miR‑195‑5p regulates multi‑drug resistance of gastric cancer cells via targeting ZNF139

Authors:
- Hongfeng Nie
- Jixing Mu
- Jinsheng Wang
- Yong Li
View Affiliations

Affiliations: Department of General Surgery, Fourth Hospital of Hebei Medical University, Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of General Surgery, The First Affiliated Hospital, Xingtai Medical College, Xingtai, Hebei 054001, P.R. China
Published online on: June 25, 2018 https://doi.org/10.3892/or.2018.6524
Pages: 1370-1378
Copyright: © Nie 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

Gastric cancer (GC) is one of the most common malignant tumors with a high mortality rate. Reversing the multi‑drug resistance (MDR) of GC offers the potential for significant enhancement of the effect of chemotherapy and improvement of prognosis. Aberrant microRNA expression can attribute to the pathogenesis of GC. However, the effects of microRNA (miR)‑195‑5p on the MDR of GC cells remains to be fully elucidated. In the present study, the effect of miR‑195‑5p in regulating the MDR of GC cells was investigated. Reverse transcription quantitative‑polymerase chain reaction was used to analyze the levels of miR‑195‑5p in GC cells. Western blot analysis was performed to analyze the protein levels of ZNF139, P‑gp, BCL‑2 and MRP1. The chemosensitivity of GC cells was determined by MTT. The results showed that the expression of miR‑195‑5p was decreased in poorly differentiated GC tissues with a higher chemosensitivity. The overexpression of miR‑195‑5p promoted the chemosensitivity of GC cells. Bioinformatics analysis indicated that Zing finger 139 (ZNF139) was a target of miR‑195‑5p. miR‑195‑5p negatively regulated the expression of ZNF139 by binding to its 3'‑untranslated region. The silencing of ZNF139 promoted the chemosensitivity of GC cells, and the downregulation of ZNF139 reversed the effect of miR‑195‑5p inhibitor on the chemosensitivity of GC cells. In conclusion, miR‑195‑5p regulated the MDR of GC cells via targeting ZNF139.

View Figures

View References

1	Barra WF, Moreira FC, Pereira Cruz AM, Khayat AS, Calcagno DQ, Carneiro Dos Santos NP, Mascarenhas Junior RW, Thomaz Araújo TM, Ishak G, Demachki S and Rodríguez Burbano RM: GEJ cancers: Gastric or esophageal tumors? searching for the answer according to molecular identity. Oncotarget. 8:104286–104294. 2017. View Article : Google Scholar : PubMed/NCBI
2	Cunningham SC, Kamangar F, Kim MP, Hammoud S, Haque R, Maitra A, Montgomery E, Heitmiller RE, Choti MA, Lillemoe KD, et al: Survival after gastric adenocarcinoma resection: Eighteen-year experience at a single institutuion. J Gastrointest Surg. 9:718–725. 2005. View Article : Google Scholar : PubMed/NCBI
3	Hwang JH: Understanding gastric cancer risk factors: We need to close the gap. Gut Liver. 12:1–2. 2018. View Article : Google Scholar : PubMed/NCBI
4	Peng PL, Zhou XY, Yi GD, Chen PF, Wang F and Dong WG: Identification of a novel gene pairs signature in the prognosis of gastric cancer. Cancer Med. 7:344–350. 2018. View Article : Google Scholar : PubMed/NCBI
5	Nienhüser H and Schmidt T: Angiogenesis and anti-angiogenic therapy in gastric cancer. Int J Mol Sci. 19:E432017. View Article : Google Scholar : PubMed/NCBI
6	Fan L, Tan B, Li Y, Zhao Q, Yuan H, Liu Y, Wang D and Zhang Z: Upregulation of miR185 promotes apoptosis of the human gastric cancer cell line MGC803. Mol Med Rep. 17:3115–3122. 2018.PubMed/NCBI
7	Huang J, He Y, McLeod HL, Xie Y, Xiao D, Hu H, Chen P, Shen L, Zeng S, Yin X, et al: miR-302b inhibits tumorigenesis by targeting EphA2 via Wnt/β-catenin/EMT signaling cascade in gastric cancer. BMC Cancer. 17:8862017. View Article : Google Scholar : PubMed/NCBI
8	Huang T, Zhou Y, Zhang J, Wong CC, Li W, Kwan JSH, Yang R, Chan AKY, Dong Y, Wu F, et al: SRGAP1, a crucial target of miR-340 and miR-124, functions as a potential oncogene in gastric tumorigenesis. Oncogene. 37:1159–117. 2018. View Article : Google Scholar : PubMed/NCBI
9	Qu Y, Zhang H, Sun W, Han Y, Li S, Qu Y, Ying G and Ba Y: MiR-155 promotes gastric cancer growth and invasion by negatively regulating transforming growth factor β receptor 2. Cancer Sci. 109:618–62. 2018. View Article : Google Scholar : PubMed/NCBI
10	Shrestha S, Yang CD, Hong HC, Chou CH, Tai CS, Chiew MY, Chen WL, Weng SL, Chen CC, Chang YA, et al: : Integrated MicroRNA-mRNA analysis reveals miR-204 inhibits cell proliferation in gastric cancer by targeting CKS1BCXCL1GPRC5A. Int J Mol Sci. 19:E872017. View Article : Google Scholar : PubMed/NCBI
11	Wang T, Ren Y, Liu R, Ma J, Shi Y, Zhang L and Bu R: miR-195-5p suppresses the proliferation, migration, and invasion of oral squamous cell carcinoma by targeting TRIM14. Biomed Res Int. 2017:73781482017. View Article : Google Scholar : PubMed/NCBI
12	Yu S, Jing L, Yin XR, Wang MC, Chen YM, Guo Y, Nan KJ and Han LL: MiR-195 suppresses the metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by inhibiting YAP. Oncotarget. 8:99757–99771. 2017.PubMed/NCBI
13	He B, Yan F and Wu C: Overexpressed miR-195 attenuated immune escape of diffuse large B-cell lymphoma by targeting PD-L1. Biomed Pharmacother. 98:95–101. 2018. View Article : Google Scholar : PubMed/NCBI
14	Hong Z, Zhang R and Qi H: Diagnostic and prognostic relevance of serum miR-195 in pediatric acute myeloid leukemia. Cancer Biomark. 21:269–275. 2018. View Article : Google Scholar : PubMed/NCBI
15	Liu Y, Liu J, Wang L, Yang X and Liu X: MicroRNA195 inhibits cell proliferation, migration and invasion in laryngeal squamous cell carcinoma by targeting ROCK1. Mol Med Rep. 16:7154–7162. 2017. View Article : Google Scholar : PubMed/NCBI
16	Qattan A, Intabli H, Alkhayal W, Eltabache C, Tweigieri T and Amer SB: Robust expression of tumor suppressor miRNA's let-7 and miR-195 detected in plasma of Saudi female breast cancer patients. BMC Cancer. 17:7992017. View Article : Google Scholar : PubMed/NCBI
17	Fléjou JF: WHO classification of digestive tumors: The fourth edition. Ann Pathol. 31 Suppl 5:S27–S31. 2011.(In French). View Article : Google Scholar : PubMed/NCBI
18	Capes-Davis A, Theodosopoulos G, Atkin I, Drexler HG, Kohara A, Macleod RA, Master JR, Nakamura Y, Reid YA, Reddel RR and Freshney RI: Check your cultures! A list of cross-contaminated or misidentified cell lines. Int J Cancer. 127:1–8. 2010. View Article : Google Scholar : PubMed/NCBI
19	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2^−ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
20	Li Y, Tan BB, Zhao Q, Fan LQ, Liu Y and Wang D: Regulatory mechanism of ZNF139 in multi-drug resistance of gastric cancer cells. Mol Biol Rep. 41:3603–3610. 2014. View Article : Google Scholar : PubMed/NCBI
21	Nie HF, Li Y, Li ZX, Mu JX and Wang JS: Effects of ZNF139 on gastric cancer cells and mice with gastric tumors. Oncol Lett. 12:2550–2554. 2016. View Article : Google Scholar : PubMed/NCBI
22	Xu W, Yang Z and Lu N: Molecular targeted therapy for the treatment of gastric cancer. J Exp Clin Cancer Res. 35:12016. View Article : Google Scholar : PubMed/NCBI
23	Chen S, Wang L, Yao X, Chen H, Xu C, Tong L, Shah A, Huang T, Chen G, Chen J, et al: miR-195-5p is critical in REGγ-mediated regulation of wnt/β-catenin pathway in renal cell carcinoma. Oncotarget. 8:63986–64000. 2017.PubMed/NCBI
24	Stefan K, Schmitt SM and Wiese M: 9-Deazapurines as broad-spectrum inhibitors of the ABC transport proteins P-glycoprotein, multidrug resistance-associated protein 1, and breast cancer resistance protein. J Med Chem. 60:8758–8780. 2017. View Article : Google Scholar : PubMed/NCBI
25	Wang Y, Wang X, Zhao H, Liang B and Du Q: Clusterin confers resistance to TNF-alpha-induced apoptosis in breast cancer cells through NF-kappaB activation and Bcl-2 overexpression. J Chemother. 24:348–357. 2012. View Article : Google Scholar : PubMed/NCBI
26	Tomek M, Akiyama T and Dass CR: Role of Bcl-2 in tumour cell survival and implications for pharmacotherapy. J Pharm Pharmacol. 64:1695–1702. 2012. View Article : Google Scholar : PubMed/NCBI
27	Jen J and Wang YC: Zinc finger proteins in cancer progression. J Biomed Sci. 23:532016. View Article : Google Scholar : PubMed/NCBI