Smad3-related miRNAs regulated oncogenic TRIB2 promoter activity to effectively suppress lung adenocarcinoma growth.
Smad3-related miRNAs regulated oncogenic TRIB2 promoter activity to effectively suppress lung adenocarcinoma growth.
复制标题
Smad3 相关 miRNA 调节致癌 TRIB2 启动子活性，有效抑制肺腺癌生长
DOI：
10.1038/cddis.2016.432
复制
发表时间：
2016-12-22
影响因子：
9
通讯作者：
Xie SY
中科院分区：
文献类型：
--
作者：
Zhang YX;Yan YF;Liu YM;Li YJ;Zhang HH;Pang M;Hu JX;Zhao W;Xie N;Zhou L;Wang PY;Xie SY
MicroRNAs (miRNAs) and Smad3, as key transcription factors in transforming growth factor-β1 (TGF-β1) signaling, help regulate various physiological and pathological processes. We investigated the roles of Smad3-regulated miRNAs with respect to lung adenocarcinoma cell apoptosis, proliferation, and metastasis. We observed that Smad3 and phospho-SMAD3 (p-Smad3) were decreased in miR-206- (or miR-140)-treated cells and there might be a feedback loop between miR-206 (or miR-140) and TGF-β1 expression. Smad3-related miRNAs affected tribbles homolog 2 (TRIB2) expression by regulating trib2 promoter activity through the CAGACA box. MiR-206 and miR-140 inhibited lung adenocarcinoma cell proliferation in vitro and in vivo by suppressing p-Smad3/Smad3 and TRIB2. Moreover, lung adenocarcinoma data supported a suppressive role for miR-206/miR-140 and an oncogenic role for TRIB2—patients with higher TRIB2 levels had poorer survival. In summary, miR-206 and miR-140, as tumor suppressors, induced lung adenocarcinoma cell death and inhibited cell proliferation by modifying oncogenic TRIB2 promoter activity through p-Smad3. MiR-206 and miR-140 also suppressed lung adenocarcinoma cell metastasis in vitro and in vivo by regulating EMT-related factors.
