title: NR2F2 inhibits Smad7 expression and promotes TGF-β-dependent epithelial-mesenchymal transition of CRC via transactivation of miR-21.
abstract: 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.
authors.affiliation: Department of Radiotherapy, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, PR China; Center of Radiotherapy, Shaanxi Provincial Tumor Hospital, Xi'an, Shaanxi 710061, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Oncology, Shaanxi Provincial Tumor Hospital, Xi'an, Shaanxi 710061, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Nie
authors.affiliation: Center of Radiotherapy, Shaanxi Provincial Tumor Hospital, Xi'an, Shaanxi 710061, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.affiliation: Center of Radiotherapy, Shaanxi Provincial Tumor Hospital, Xi'an, Shaanxi 710061, PR China.
authors.forename: Qiufang
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Gastroentology, The Third Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710068, PR China. Electronic address: guoxueyanxajt@163.com.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Guo
mesh_terms: D051837:COUP Transcription Factor II / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D012007:Rectum / Q000378:metabolism / Q000473:pathology; D051906:Smad7 Protein / Q000235:genetics*; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D051837:COUP Transcription Factor II; D035683:MicroRNAs; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; C524940:MIRN21 microRNA, human; C497806:SMAD7 protein, human; C095569:NR2F2 protein, human
keywords: CRC; EMT; NR2F2; Smad7; miR-21