NR2F2 inhibits Smad7 expression and promotes TGF-β-dependent epithelial-mesenchymal transition of CRC via transactivation of miR-21

作者：Wang, Hao; Nie, Lei; Wu, Lei; Liu, Qiufang; Guo, Xueyan^*

来源：Biochemical and Biophysical Research Communications, 2017, 485(1): 181-188.

DOI：10.1016/j.bbrc.2017.02.049

• NR2F2
• miR-21
• Smad7
• EMT
• CRC

Metastasis is one of the most decisive factors influencing CRC patient prognosis and current studies suggest that a molecular mechanism known as EMT broadly regulates cancer metastasis. NR2F2 is a key molecule in the development of CRC, but the roles and underlying mechanisms of NR2F2 in TGF-beta induced EMT in CRC remain largely unknown. In the current study, we were interested to examine the role of NR2F2 in the TGF-beta-induced EMT in CRC. Here, we found NR2F2 was upregulated in CRC cells and promotes TGF-beta-induced EMT in CRC. Using comparative miRNA profiling TGF-beta pre-treated CRC cells in which NR2F2 had been knocked down with that of control cells, we identified miR-21 as a commonly downregulated miRNA in HT29 cells treated with TGF-beta and NR2F2 siRNA, and its downregulation inhibiting migration and invasion of CRC cells. Moreover, we found NR2F2 could transcriptional activated miR-21 expression by binding to miR-21 promoter in HT29 by ChIP and luciferase assay. In the last, our data demonstrated that Smad7 was the direct target of miR-21 in CRC cells. Thus, NR2F2 could promote TGF-beta-induced EMT and inhibit Smad7 expression via transactivation of miR-21, and NR2F2 may be a new common therapeutic target for CRC.

• 出版日期2017-3-25
• 单位陕西省肿瘤医院; 西安交通大学