miR-193a-3p Functions as a Tumor Suppressor in Lung Cancer by Down-regulating ERBB4
miR-193a-3p Functions as a Tumor Suppressor in Lung Cancer by Down-regulating ERBB4
复制标题
miR-193a-3p 通过下调 ERBB4 作为肺癌肿瘤抑制因子。
DOI：
10.1074/jbc.m114.621409
复制
发表时间：
2015-01-09
影响因子：
4.8
通讯作者：
Chen, Xi
中科院分区：
文献类型：
--
作者：
Liang, Hongwei;Liu, Minghui;Chen, Xi
ERBB4, one of four ErbB receptor tyrosine kinase family members, plays an important role in the etiology and progression of lung cancer. In this study, we found that the ERBB4 protein levels were consistently up-regulated in lung cancer tissues, whereas the mRNA levels varied randomly, suggesting that a post-transcriptional mechanism was involved in regulating ERBB4 expression. Because microRNAs are powerful post-transcriptional regulators of gene expression, we used bioinformatic analyses to search for microRNAs that can potentially target ERBB4. Weidentified specific targeting sites for miR-193a-3p in the 3'-UTR of ERBB4. We further identified an inverse correlation between miR-193a-3p levels and ERBB4 protein levels, but not mRNA levels, in lung cancer tissue samples. By overexpressing or knocking down miR-193a-3p in lung cancer cells, we experimentally confirmed that miR-193a-3p directly recognizes the 3'-UTR of the ERBB4 transcript and regulates ERBB4 expression. Furthermore, the biological consequences of the targeting of ERBB4 by miR-193a-3p were examined in vitro via cell proliferation, invasion, and apoptosis assays and in vivo using a mouse xenograft tumor model. We demonstrated that the repression of ERBB4 by miR-193a-3p suppressed proliferation and invasion and promoted apoptosis in lung cancer cells and that miR-193a-3p exerted an anti-tumor effect by negatively regulating ERBB4 in xenograft mice. Taken together, our findings provide the first clues regarding the role of miR-193a-3p as a tumor suppressor in lung cancer through the inhibition of ERBB4 translation.
