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miR ‐494 acts as an anti‐oncogene in gastric carcinoma by targeting c‐myc
Author(s) -
He Weiling,
Li Yuhuang,
Chen Xinlin,
Lu Liya,
Tang Bin,
Wang Zhixiong,
Pan Yunbao,
Cai Shirong,
He Yulong,
Ke Zunfu
Publication year - 2014
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.12558
Subject(s) - oncogene , cancer research , microrna , luciferase , cell growth , cancer , microbiology and biotechnology , cell cycle , biology , medicine , cell culture , gene , transfection , biochemistry , genetics
Background We recently showed that miR ‐494 was downregulated in gastric carcinoma ( GC ). The objectives of this study were to determine the role of miR ‐494 in GC malignancy and to identify its target genes. Methods Real‐time polymerase chain reaction was employed to quantify the expression level of miR ‐494 and c‐myc in gastric cancer tissues. Bioinformatics was used to predict the downstream target genes of miR ‐494, which were confirmed by luciferase and RNA immunoprecipitation assays. Cell functional analyses and a xenograft mouse model were used to evaluate the role of miR ‐494 in malignancy. Results miR ‐494 was downregulated in human GC tissues and in GC cells and was negatively correlated with c‐myc expression. High level of c‐myc or low level of mi R ‐494 correlated with poor prognosis. The miR ‐494‐binding site in the c‐myc 3′ untranslated region was predicted using TargetScan and was confirmed by the luciferase assay. Additionally, c‐myc and miR ‐494 were enriched in coimmunoprecipitates with tagged A rgonaute2 proteins in cells overexpressing miR ‐494. Furthermore, a miR ‐494 mimic significantly downregulated endogenous c‐myc expression, which may contribute to the delayed G 1/ S transition, decreased synthesis phase bromodeoxyuridine incorporation, and impaired cell growth and colony formation; on the other hand, treatment with a miR ‐494 inhibitor displayed the opposite effects. Reduced tumor burden and decreased cell proliferation were observed following the delivery of miR ‐494 into xenograft mice. Conclusion miR ‐494 is downregulated in human GC and acts as an anti‐oncogene by targeting c‐myc. miR ‐494 plays a role in the pathogenesis of gastric cancer in a recessive fashion.