Downregulated miRNA‑1269a variant (rs73239138) decreases the susceptibility to gastric cancer via targeting ZNF70

Li,Wenshuai; Zhang,Huilu; Min,Pei; Zhu,Jie; Xu,Diannan; Jiang,Weiru; Ma,Yanyun; Qiu,Jigang; Xu,Weihong; Chen,Jian; Zhang,Mingqing; Li,Min; Yang,Dongqin; Shi,Jianping; Zhang,Jun; Liu,Jie

doi:10.3892/ol.2017.7091

Downregulated miRNA‑1269a variant (rs73239138) decreases the susceptibility to gastric cancer via targeting ZNF70

Authors:
- Wenshuai Li
- Huilu Zhang
- Pei Min
- Jie Zhu
- Diannan Xu
- Weiru Jiang
- Yanyun Ma
- Jigang Qiu
- Weihong Xu
- Jian Chen
- Mingqing Zhang
- Min Li
- Dongqin Yang
- Jianping Shi
- Jun Zhang
- Jie Liu
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Affiliations: Department of Digestive Diseases, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Digestive Diseases, Southeast Hospital, Xiamen University, Zhangzhou, Fujian 363000, P.R. China, Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, P.R. China, Department of General Surgery, Huadong Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Clinical Laboratory, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 20050, P.R. China, Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China, Department of Clinical Laboratory, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200240, P.R. China, Department of Digestive Diseases, Shanghai Pudong Hospital, Fudan University, Shanghai 201399, P.R. China
Published online on: September 28, 2017 https://doi.org/10.3892/ol.2017.7091
Pages: 6345-6354
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although emerging evidence has indicated that single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) are associated with susceptibility to gastric cancer, a limited number of studies have revealed the underlying molecular mechanisms. In the present study, the results suggested that miR‑1269a rs73239138 has a role in decreasing the risk of gastric cancer. The level of miR‑1269a variant expression was significantly downregulated compared with the wild‑type miR‑1269a in the gastric cells (Fig. 1). Furthermore, overexpression of miR‑1269a inhibited apoptosis of gastric cancer cells. Expression of the miR‑1269a variant inhibited the function of miR‑1269a by increasing the apoptotic rate and the expression of Bik, Bim and Bak was upregulated consistently. In addition, zinc‑finger protein 70 (ZNF70) was identified to be a target gene of miR‑1269a, which was downregulated by miR‑1269a and upregulated by miR‑1269a variant. ZNF70 was indicated to exert a role as a tumor suppressor in gastric cancer. To the best our knowledge, the present study for the first time highlights a critical role of miR‑1269a variant rs73239138 in decreasing the susceptibility to gastric cancer by downregulating its expression and targeting ZNF70, which promotes apoptosis of gastric cancer cells. This SNP is indicated to serve as a potential biomarker and therapeutic target for gastric cancer.

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1	Nagini S: Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol. 4:156–169. 2012. View Article : Google Scholar : PubMed/NCBI
2	PDQ Screening and Prevention Editorial Board: Stomach (Gastric) Cancer Prevention (PDQ®): Health Professional Version, . PDQ Cancer Information Summaries. National Cancer Institute (US); Bethesda (MD): 2002
3	Li J, Zhang S, Liu J, Shao M and Chen L: Review of clinical investigation on recurrence of gastric cancer following curative resection. Chin Med J. 125:1479–1495. 2012.PubMed/NCBI
4	Roukos DH and Kappas AM: Limitations in controlling risk for recurrence after curative surgery for advanced gastric cancer are now well-explained by molecular-based mechanisms. Ann Surg Oncol. 8:620–621. 2001. View Article : Google Scholar : PubMed/NCBI
5	Bartel DP: MicroRNAs: Target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI
6	Zhang R and Su B: Small but influential: The role of microRNAs on gene regulatory network and 3′UTR evolution. J Genet Genomics. 36:1–6. 2009. View Article : Google Scholar : PubMed/NCBI
7	Ambros V: The functions of animal microRNAs. Nature. 431:350–355. 2004. View Article : Google Scholar : PubMed/NCBI
8	Song JH and Meltzer SJ: MicroRNAs in pathogenesis, diagnosis, and treatment of gastroesophageal cancers. Gastroenterology. 143(35–47): e22012.
9	Mizuno K, Seki N, Mataki H, Matsushita R, Kamikawaji K, Kumamoto T, Takagi K, Goto Y, Nishikawa R, Kato M, et al: Tumor-suppressive microRNA-29 family inhibits cancer cell migration and invasion directly targeting LOXL2 in lung squamous cell carcinoma. Int J Oncol. 48:450–460. 2016. View Article : Google Scholar : PubMed/NCBI
10	Song S and Ajani JA: The role of microRNAs in cancers of the upper gastrointestinal tract. Nat Rev Gastroenterol Hepatol. 10:109–118. 2013. View Article : Google Scholar : PubMed/NCBI
11	Chung CC and Chanock SJ: Current status of genome-wide association studies in cancer. Hum Genet. 130:59–78. 2011. View Article : Google Scholar : PubMed/NCBI
12	Zheng H, Song F, Zhang L, Yang D, Ji P, Wang Y, Almeida M, Calin GA, Hao X, Wei Q, et al: Genetic variants at the miR-124 binding site on the cytoskeleton-organizing IQGAP1 gene confer differential predisposition to breast cancer. Int J Oncol. 38:1153–1161. 2011.PubMed/NCBI
13	Saunders MA, Liang H and Li WH: Human polymorphism at microRNAs and microRNA target sites. Proc Natl Acad Sci USA. 104:pp. 3300–3305. 2007, View Article : Google Scholar : PubMed/NCBI
14	Yang XW, Shen GZ, Cao LQ, Jiang XF, Peng HP, Shen G, Chen D and Xue P: MicroRNA-1269 promotes proliferation in human hepatocellular carcinoma via downregulation of FOXO1. BMC Cancer. 14:9092014. View Article : Google Scholar : PubMed/NCBI
15	Bu P, Wang L, Chen KY, Rakhilin N, Sun J, Closa A, Tung KL, King S, Kristine Varanko A, Xu Y, et al: miR-1269 promotes metastasis and forms a positive feedback loop with TGF-β. Nat Commun. 6:68792015. View Article : Google Scholar : PubMed/NCBI
16	Persson H, Kvist A, Rego N, Staaf J, Vallon-Christersson J, Luts L, Loman N, Jonsson G, Naya H, Hoglund M, et al: Identification of new microRNAs in paired normal and tumor breast tissue suggests a dual role for the ERBB2/Her2 gene. Cancer Res. 71:78–86. 2011. View Article : Google Scholar : PubMed/NCBI
17	Ma Y, Wang R, Zhang J, Li W, Gao C, Liu J and Wang J: Identification of miR-423 and miR-499 polymorphisms on affecting the risk of hepatocellular carcinoma in a large-scale population. Genet Test Mol Biomarkers. 18:516–524. 2014. View Article : Google Scholar : PubMed/NCBI
18	Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, et al: Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium. Nat Genet. 25:25–29. 2000. View Article : Google Scholar : PubMed/NCBI
19	Dupuy D, Bertin N, Hidalgo CA, Venkatesan K, Tu D, Lee D, Rosenberg J, Svrzikapa N, Blanc A, Carnec A, et al: Genome-scale analysis of in vivo spatiotemporal promoter activity in Caenorhabditis elegans. Nat Biotechnol. 25:663–668. 2007. View Article : Google Scholar : PubMed/NCBI
20	Kanehisa M, Goto S, Kawashima S, Okuno Y and Hattori M: The KEGG resource for deciphering the genome. Nucleic Acids Res. 32:D277–D280. 2004. View Article : Google Scholar : PubMed/NCBI
21	Yi M, Horton JD, Cohen JC, Hobbs HH and Stephens RM: WholePathwayScope: A comprehensive pathway-based analysis tool for high-throughput data. BMC Bioinformatics. 7:302006. View Article : Google Scholar : PubMed/NCBI
22	Draghici S, Khatri P, Tarca AL, Amin K, Done A, Voichita C, Georgescu C and Romero R: A systems biology approach for pathway level analysis. Genome Res. 17:1537–1545. 2007. View Article : Google Scholar : PubMed/NCBI
23	Xie L, Shen Y, Franke D, Sebastian V, Bawendi MG and Jensen KF: Characterization of indium phosphide quantum dot growth intermediates using MALDI-TOF mass spectrometry. J Am Chem Soc. 2016. View Article : Google Scholar
24	Wang Y, Tang N, Hui T, Wang S, Zeng X, Li H and Ma J: Identification of endogenous reference genes for RT-qPCR analysis of plasma microRNAs levels in rats with acetaminophen-induced hepatotoxicity. J Appl Toxicol. 33:1330–1336. 2013.PubMed/NCBI
25	Zhang X, Nie Y, Du Y, Cao J, Shen B and Li Y: MicroRNA-181a promotes gastric cancer by negatively regulating tumor suppressor KLF6. Tumour Biol. 33:1589–1597. 2012. View Article : Google Scholar : PubMed/NCBI
26	Wang S, Lv C, Jin H, Xu M, Kang M, Chu H, Tong N, Wu D, Zhu H, Gong W, et al: A common genetic variation in the promoter of miR-107 is associated with gastric adenocarcinoma susceptibility and survival. Mutat Res. 769:35–41. 2014. View Article : Google Scholar : PubMed/NCBI
27	Fu B, Song P, Lu M, Wang B and Zhao Q: The association between miR-146a gene rs2910164 polymorphism and gastric cancer risk: A meta-analysis. Biomed Pharmacother. 68:923–928. 2014. View Article : Google Scholar : PubMed/NCBI
28	Cai M, Zhang Y, Ma Y, Li W, Min P, Qiu J, Xu W, Zhang M, Li M, Li L, et al: Association between microRNA-499 polymorphism and gastric cancer risk in Chinese population. Bull Cancer. 102:973–978. 2015. View Article : Google Scholar : PubMed/NCBI
29	Laity JH, Lee BM and Wright PE: Zinc finger proteins: New insights into structural and functional diversity. Curr Opin Struct Biol. 11:39–46. 2001. View Article : Google Scholar : PubMed/NCBI
30	Cohen PA, Donini CF, Nguyen NT, Lincet H and Vendrell JA: The dark side of ZNF217, a key regulator of tumorigenesis with powerful biomarker value. Oncotarget. 6:41566–41581. 2015. View Article : Google Scholar : PubMed/NCBI
31	Ravasi T, Suzuki H, Cannistraci CV, Katayama S, Bajic VB, Tan K, Akalin A, Schmeier S, Kanamori-Katayama M, Bertin N, et al: An atlas of combinatorial transcriptional regulation in mouse and man. Cell. 140:744–752. 2010. View Article : Google Scholar : PubMed/NCBI