These authors contributed equally to this work.
miR-494 acts as an anti-oncogene in gastric carcinoma by targeting c-myc
Version of Record online: 15 JUL 2014
© 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 29, Issue 7, pages 1427–1434, July 2014
How to Cite
He, W., Li, Y., Chen, X., Lu, L., Tang, B., Wang, Z., Pan, Y., Cai, S., He, Y. and Ke, Z. (2014), miR-494 acts as an anti-oncogene in gastric carcinoma by targeting c-myc. Journal of Gastroenterology and Hepatology, 29: 1427–1434. doi: 10.1111/jgh.12558
Conflict of interest
The authors have no conflicts of interest to declare.
- Issue online: 15 JUL 2014
- Version of Record online: 15 JUL 2014
- Accepted manuscript online: 26 FEB 2014 03:57AM EST
- Manuscript Accepted: 20 JAN 2014
- National Natural Science Foundation of China. Grant Numbers: 30973395, 81172337, 31271444, 81201726
- Municipal Medicine Science and Technology Foundation of Guangzhou. Grant Number: 201102A212012
- Science and Technology Development Program of Guangdong. Grant Number: 2012B031800115
- Science Novel Program of Guangdong Education Department. Grant Number: A2003165
- gastric cancer;
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.
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.
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 miR-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 Argonaute2 proteins in cells overexpressing miR-494. Furthermore, a miR-494 mimic significantly downregulated endogenous c-myc expression, which may contribute to the delayed G1/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.
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.