MiR-382 inhibits cell growth and invasion by targeting NR2F2 in colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. MiR-382 has been found to have a decreased expression and the ability to suppress tumorigenesis in certain cancers. However, the role of miR-382 in CRC has not been sufficiently investigated. NR2F2 (also known as COUP-TFII), a member of the steroid/thyroid receptor superfamily, is often aberrantly activated in various tumors, but it is currently unclear whether NR2F2 may be a target of miR-382. In the present study, we investigated the role of miR-382 in CRC and identified the regulation of NR2F2 by miR-382. We observed that miR-382 was aberrantly downregulated in CRC. Transfection with miR-382 mimics impeded the growth, migration, and invasion of CRC cells. The direct binding of miR-382 to the 3' untranslated region (3' UTR) of NR2F2 was confirmed using a luciferase reporter gene assay. We showed that the relative expression levels of NR2F2 were significantly higher in CRC tissues compared with normal adjacent mucosa. A Kaplan-Meier analysis indicated that patients with high NR2F2 expression had a poor overall survival. Knockdown of NR2F2 inhibited CRC cell growth, migration, and invasion. Ectopic expression of NR2F2 mitigated miR-382 suppression of CRC cell proliferation, migration, and invasion. In conclusion, the present study describes a potential mechanism underlying a miR-382/NR2F2 link contributing to CRC development. Our results demonstrate that miR-382 represents a potential strategy against CRC. © 2016 Wiley Periodicals, Inc.

Zhou B ，Song J ，Han T ，Huang M ，Jiang H ，Qiao H ，Shi J ，Wang Y ... -  《-》

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

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-β induced EMT in CRC remain largely unknown. In the current study, we were interested to examine the role of NR2F2 in the TGF-β-induced EMT in CRC. Here, we found NR2F2 was upregulated in CRC cells and promotes TGF-β-induced EMT in CRC. Using comparative miRNA profiling TGF-β 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-β 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-β-induced EMT and inhibit Smad7 expression via transactivation of miR-21, and NR2F2 may be a new common therapeutic target for CRC.

Wang H ，Nie L ，Wu L ，Liu Q ，Guo X ... -  《-》

miR-182 promotes cell growth and invasion by targeting forkhead box F2 transcription factor in colorectal cancer.

Zhang Y ，Wang X ，Wang Z ，Tang H ，Fan H ，Guo Q ... -  《-》

The miR-106b/NR2F2-AS1/PLEKHO2 Axis Regulates Migration and Invasion of Colorectal Cancer through the MAPK Pathway.

Liu S ，An G ，Cao Q ，Li T ，Jia X ，Lei L ... -  《-》

MiR-622 inhibited colorectal cancer occurrence and metastasis by suppressing K-Ras.

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide, with many oncogenes and anti-oncogenes involved. MicroRNAs (miRNAs) are a class of small, noncoding RNA molecules that can adjust downstream targets. Accumulating evidence has revealed that microRNAs govern the occurrence and development of cancer. Here, we studied the role of miR-622 in CRC and clarified the underlying mechanism. We detected that miR-622 was down-regulated in colorectal tumor tissues and cell lines and that miR-622 was lower in metastatic CRC tissues compared with that in non-metastatic specimens. Furthermore, we confirmed that miR-622 inhibited tumor proliferation and migration in vitro. Through dual-luciferase reporter assay, we found kirsten rat sarcoma (K-Ras) gene was the direct target of miR-622. More importantly, K-Ras overexpression can rescue the inhibitory effect of miR-622 on CRC development. All these data were validated in colon xenograft tumor model. MiR-622-K-Ras signal pathway was a potentially new direction in the development of screening target and therapeutic treatments for CRC. © 2015 Wiley Periodicals, Inc.

Fang Y ，Sun B ，Li Z ，Chen Z ，Xiang J ... -  《-》