Low expression levels of plasma miR‑141 are associated with susceptibility to gastric cancer

Wang,Tianxi; Zhang,Jun; Tian,Jingjing; Hu,Shasha; Wei,Rongna; Cui,Lihong

doi:10.3892/ol.2019.10390

Low expression levels of plasma miR‑141 are associated with susceptibility to gastric cancer

Authors:
- Tianxi Wang
- Jun Zhang
- Jingjing Tian
- Shasha Hu
- Rongna Wei
- Lihong Cui
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Affiliations: Department of Gastroenterology, Tianjin Nankai Hospital, Nankai, Tianjin 300100, P.R. China, Department of General Medicine, Tianjin Beichen Hospital, Tianjin, 300401, P.R. China
Published online on: May 21, 2019 https://doi.org/10.3892/ol.2019.10390
Pages: 629-636
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

MicroRNAs (miRNAs/miRs) offer great potential as biomarkers for the early detection and prognosis of cancer, and the discovery of miRNAs associated with gastric cancer is required. In the present study, the differences in the plasma expression levels of miR‑141 between patients with gastric cancer and healthy controls, and the role of miR‑141 in gastric cancer cell oncogenesis were investigated. A follow‑up study of 164 patients with gastric cancer who underwent tumor resection was conducted, and comparisons with healthy control subjects were drawn. To investigate the biological functions of miR‑141, a series of in vitro and in vivo assays were conducted, including proliferation, wound‑healing and Transwell assays, and a xenograft tumor model. The results demonstrated that miR‑141 expression was significantly decreased in tumor tissues compared with in healthy tissues (P<0.05). Kaplan‑Meier analysis revealed improved survival benefits with increased miR‑141 expression (as determined using the log‑rank test, P<0.001), and multivariate Cox regression analysis revealed that patients with decreased expression levels of miR‑141 carried a greater risk of death (hazard ratio=2.352; 95% CI=1.379‑4.012; P=0.002). The downregulation of miR‑141 was also associated with WHO staging, particularly for lymph node and distant metastasis. Exogenous overexpression of miR‑141 significantly inhibited the proliferative and migratory abilities of the gastric cancer cell line BGC‑823. In vivo studies also demonstrated that exogenous overexpression of miR‑141 in BGC‑823 cells markedly reduced tumor growth in nude mice. The present study revealed that increased miR‑141 expression may be a positive prognostic factor, which may be clinically beneficial in patients with gastric cancer.

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1	Crew KD and Neugut AI: Epidemiology of gastric cancer. World J Gastroenterol. 12:354–362. 2006. View Article : Google Scholar : PubMed/NCBI
2	Song YX, Yue ZY, Wang ZN, Xu YY, Luo Y, Xu HM, Zhang X, Jiang L, Xing CZ and Zhang Y: MicroRNA-148b is frequently down-regulated in gastric cancer and acts as a tumor suppressor by inhibiting cell proliferation. Mol Cancer. 10:12011. View Article : Google Scholar : PubMed/NCBI
3	Zuberi M, Khan I, Mir R, Gandhi G, Ray PC and Saxena A: Utility of Serum miR-125b as a diagnostic and prognostic indicator and its alliance with a panel of tumor suppressor genes in epithelial ovarian cancer. PLoS One. 11:e01539022016. View Article : Google Scholar : PubMed/NCBI
4	Kinose Y, Sawada K, Nakamura K and Kimura T: The role of microRNAs in ovarian cancer. Biomed Res Int. 2014:2493932014. View Article : Google Scholar : PubMed/NCBI
5	Tilghman SL, Rhodes LV, Bratton MR, Carriere P, Preyan LC, Boue SM, Vasaitis TS, McLachlan JA and Burow ME: Phytoalexins, miRNAs and breast cancer: A review of phytochemical-mediated miRNA regulation in breast cancer. J Health Care Poor Underserved. 24 (Suppl 1):S36–S46. 2013. View Article : Google Scholar
6	Chen J, Deng S, Zhang S, Chen Z, Wu S, Cai X, Yang X, Guo B and Peng Q: The role of miRNAs in the differentiation of adipose-derived stem cells. Curr Stem Cell Res Ther. 9:268–279. 2014. View Article : Google Scholar : PubMed/NCBI
7	Du L, Borkowski R, Zhao Z, Ma X, Yu X, Xie XJ and Pertsemlidis A: A high-throughput screen identifies miRNA inhibitors regulating lung cancer cell survival and response to paclitaxel. RNA Biol. 10:1700–1713. 2013. View Article : Google Scholar : PubMed/NCBI
8	He J, Zhang JF, Yi C, Lv Q, Xie WD, Li JN, Wan G, Cui K, Kung HF, Yang J, et al: miRNA-mediated functional changes through co-regulating function related genes. PLoS One. 5:e135582010. View Article : Google Scholar : PubMed/NCBI
9	Recchiuti A and Serhan CN: Pro-resolving lipid mediators (SPMs) and their actions in regulating miRNA in novel resolution circuits in inflammation. Front Immunol. 3:2982012. View Article : Google Scholar : PubMed/NCBI
10	Wolff LJ, Wolff JA and Sebestyén MG: Effect of tissue-specific promoters and microRNA recognition elements on stability of transgene expression after hydrodynamic naked plasmid DNA delivery. Hum Gene Ther. 20:374–388. 2009. View Article : Google Scholar : PubMed/NCBI
11	Xia JH, He XP, Bai ZY and Yue GH: Identification and characterization of 63 MicroRNAs in the Asian seabass Lates calcarifer. PLoS One. 6:e175372011. View Article : Google Scholar : PubMed/NCBI
12	Vos S, Vesuna F, Raman V, van Diest PJ and van der Groep P: miRNA expression patterns in normal breast tissue and invasive breast cancers of BRCA1 and BRCA2 germ-line mutation carriers. Oncotarget. 6:32115–32137. 2015. View Article : Google Scholar : PubMed/NCBI
13	Mushtaq G, Greig NH, Anwar F, Zamzami MA, Choudhry H, Shaik MM, Tamargo IA and Kamal MA: miRNAs as circulating biomarkers for Alzheimer's disease and Parkinson's disease. Med Chem. 12:217–225. 2016. View Article : Google Scholar : PubMed/NCBI
14	Ren X, Bai X, Zhang X, Li Z, Tang L, Zhao X, Li Z, Ren Y, Wei S, Wang Q, et al: Quantitative nuclear proteomics identifies that miR-137-mediated EZH2 reduction regulates resveratrol-induced apoptosis of neuroblastoma cells. Mol Cell Proteomics. 14:316–328. 2015. View Article : Google Scholar : PubMed/NCBI
15	Wang LG, Ni Y, Su BH, Mu XR, Shen HC and Du JJ: MicroRNA-34b functions as a tumor suppressor and acts as a nodal point in the feedback loop with Met. Int J Oncol. 42:957–962. 2013. View Article : Google Scholar : PubMed/NCBI
16	Aure MR, Leivonen SK, Fleischer T, Zhu Q, Overgaard J, Alsner J, Tramm T, Louhimo R, Alnæs GI, Perälä M, et al: Individual and combined effects of DNA methylation and copy number alterations on miRNA expression in breast tumors. Genome Biol. 14:R1262013. View Article : Google Scholar : PubMed/NCBI
17	Qin W, Zhang K, Clarke K, Weiland T and Sauter ER: Methylation and miRNA effects of resveratrol on mammary tumors vs. Nutr Cancer. 66:270–277. 2014. View Article : Google Scholar : PubMed/NCBI
18	Schwarzenbach H, Nishida N, Calin GA and Pantel K: Clinical relevance of circulating cell-free microRNAs in cancer. Nat Rev Clin Oncol. 11:145–156. 2014. View Article : Google Scholar : PubMed/NCBI
19	Xu J, Cao Z, Liu W, You L, Zhou L, Wang C, Lou W, Sun B, Miao Y, Liu X, et al: Plasma miRNAs effectively distinguish patients with pancreatic cancer from controls: A multicenter study. Ann Surg. 263:1173–1179. 2016. View Article : Google Scholar : PubMed/NCBI
20	Park SM, Gaur AB, Lengyel E and Peter ME: The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 22:894–907. 2008. View Article : Google Scholar : PubMed/NCBI
21	Long ZH, Bai ZG, Song JN, Zheng Z, Li J, Zhang J, Cai J, Yao HW, Wang J, Yang YC, et al: miR-141 inhibits proliferation and migration of colorectal cancer SW480 Cells. Anticancer Res. 37:4345–4352. 2017.PubMed/NCBI
22	van Jaarsveld MT, Helleman J, Boersma AW, van Kuijk PF, van Ijcken WF, Despierre E, Vergote I, Mathijssen RH, Berns EM, Verweij J, et al: miR-141 regulates KEAP1 and modulates cisplatin sensitivity in ovarian cancer cells. Oncogene. 32:4284–4293. 2013. View Article : Google Scholar : PubMed/NCBI
23	Zhou X, Su J, Zhu L and Zhang G: Helicobacter pylori modulates cisplatin sensitivity in gastric cancer by down-regulating miR-141 expression. Helicobacter. 19:174–181. 2014. View Article : Google Scholar : PubMed/NCBI
24	Fu WF, Chen WB, Dai L, Yang GP, Jiang ZY, Pan L, Zhao J and Chen G: Inhibition of miR-141 reverses cisplatin resistance in non-small cell lung cancer cells via upregulation of programmed cell death protein 4. Eur Rev Med Pharmacol Sci. 20:2565–2572. 2016.PubMed/NCBI
25	Wang D, Ma J, Ji X, Xu F and Wei Y: miR-141 regulation of EIF4E expression affects docetaxel chemoresistance of non-small cell lung cancer. Oncol Rep. 37:608–616. 2017. View Article : Google Scholar : PubMed/NCBI
26	Tejero R, Navarro A, Campayo M, Viñolas N, Marrades RM, Cordeiro A, Ruíz-Martínez M, Santasusagna S, Molins L, Ramirez J and Monzó M: miR-141 and miR-200c as markers of overall survival in early stage non-small cell lung cancer adenocarcinoma. PLoS One. 9:e1018992014. View Article : Google Scholar : PubMed/NCBI
27	Kim YH, Kim JH, Kim H, Kim H, Lee YC, Lee SK, Shin SK, Park JC, Chung HS, Park JJ, et al: Is the recent WHO histological classification for gastric cancer helpful for application to endoscopic resection? Gastric Cancer. 19:869–875. 2016. View Article : Google Scholar : PubMed/NCBI
28	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
29	Sen Z, Zhan XK, Jing J, Yi Z and Wanqi Z: Chemosensitizing activities of cyclotides from Clitoria ternatea in paclitaxel-resistant lung cancer cells. Oncol Lett. 5:641–644. 2013. View Article : Google Scholar : PubMed/NCBI
30	Zhang S, Xin H, Li Y, Zhang D, Shi J, Yang J and Chen X: Skimmin, a coumarin from hydrangea paniculata, slows down the progression of membranous glomerulonephritis by Anti-inflammatory effects and inhibiting immune complex deposition. Evid Based Complement Alternat Med. 2013:8192962013.PubMed/NCBI
31	Kontomanolis EN and Koukourakis MI: MicroRNA: The potential regulator of endometrial carcinogenesis. Microrna. 4:18–25. 2015. View Article : Google Scholar : PubMed/NCBI
32	Fan Y, Zhou Y, Zhou X, Sun F, Gao B, Wan M, Zhou X, Sun J, Xu X, Cheng L, et al: MicroRNA 224 regulates ion transporter expression in ameloblasts to coordinate enamel mineralization. Mol Cell Biol. 35:2875–2890. 2015. View Article : Google Scholar : PubMed/NCBI
33	Hu Y, Xu K and Yagüe E: miR-218 targets survivin and regulates resistance to chemotherapeutics in breast cancer. Breast Cancer Res Treat. 151:269–280. 2015. View Article : Google Scholar : PubMed/NCBI
34	Li Q, Zhu F and Chen P: miR-7 and miR-218 epigenetically control tumor suppressor genes RASSF1A and Claudin-6 by targeting HoxB3 in breast cancer. Biochem Biophys Res Commun. 424:28–33. 2012. View Article : Google Scholar : PubMed/NCBI
35	Yang L, Xu Q, Xie H, Gu G and Jiang J: Expression of serum miR-218 in hepatocellular carcinoma and its prognostic significance. Clin Transl Oncol. 18:841–847. 2016. View Article : Google Scholar : PubMed/NCBI
36	Jiang Z, Song Q, Yang S, Zeng R, Li X, Jiang C, Ding W, Zhang J and Zheng Y: Serum microRNA-218 is a potential biomarker for esophageal cancer. Cancer Biomark. 15:381–389. 2015. View Article : Google Scholar : PubMed/NCBI
37	Xin SY, Feng XS, Zhou LQ, Sun JJ, Gao XL and Yao GL: Reduced expression of circulating microRNA-218 in gastric cancer and correlation with tumor invasion and prognosis. World J Gastroenterol. 20:6906–6911. 2014. View Article : Google Scholar : PubMed/NCBI
38	Zhang XL, Shi HJ, Wang JP, Tang HS, Wu YB, Fang ZY, Cui SZ and Wang LT: MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin. World J Gastroenterol. 20:11347–11355. 2014. View Article : Google Scholar : PubMed/NCBI