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微小RNA-449a通过靶向Bcl-2在胃腺癌中发挥肿瘤抑制作用。

microRNA-449a functions as a tumor-suppressor in gastric adenocarcinoma by targeting Bcl-2.

作者信息

Wei Bin, Song Ying, Zhang Yonghong, Hu Mingjun

机构信息

Department of Gastroenterology, Xi'an First Hospital, Xi'an, Shaanxi 710002, P.R. China.

出版信息

Oncol Lett. 2013 Dec;6(6):1713-1718. doi: 10.3892/ol.2013.1609. Epub 2013 Oct 9.

Abstract

microRNAs (miRNAs or miRs) may function as oncogenes or tumor suppressors. The present study identified that miR-449a was downregulated in human gastric cancer. The overexpression of miR-449a inhibited gastric adenocarcinoma cell growth and promoted cell apoptosis in the MGC-803 and SGC-7901 gastric adenocarcinoma cell lines. Subsequently, Bcl-2 was identified as a potential miR-449a target by bioinformatics analysis. It was also shown that Bcl-2 was negatively regulated by miR-449a at the post-transcriptional level, via a specific target site within the 3'-untranslated region (3'UTR), by luciferase reporter assay. The expression of miR-449a induced cell apoptosis, as observed by TdT-mediated dUTP nick end labeling and caspase 3/7 assays, and was rescued by Bcl-2 expression. Therefore, these observations indicate that miR-449a acts as a tumor suppressor by targeting the Bcl-2 gene and that it promotes gastric adenocarcinoma cell apoptosis via Bcl-2. The findings of this study contribute to or current understanding of the functions of miR-449a in gastric adenocarcinoma.

摘要

微小RNA(miRNA或miR)可能作为癌基因或肿瘤抑制因子发挥作用。本研究发现miR-449a在人类胃癌中表达下调。miR-449a的过表达抑制了胃腺癌细胞的生长,并促进了MGC-803和SGC-7901胃腺癌细胞系的细胞凋亡。随后,通过生物信息学分析确定Bcl-2是miR-449a的潜在靶标。荧光素酶报告基因检测还表明,miR-449a在转录后水平通过3'-非翻译区(3'UTR)内的特定靶位点对Bcl-2进行负调控。如通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记和半胱天冬酶3/7检测所观察到的,miR-449a的表达诱导细胞凋亡,而Bcl-2的表达可挽救这种凋亡。因此,这些观察结果表明,miR-449a通过靶向Bcl-2基因发挥肿瘤抑制作用,并通过Bcl-2促进胃腺癌细胞凋亡。本研究结果有助于我们目前对miR-449a在胃腺癌中功能的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87dd/3833858/551150cdee61/OL-06-06-1713-g00.jpg

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