title: microRNA-200c modulates the epithelial-to-mesenchymal transition in human renal cell carcinoma metastasis.
abstract: microRNAs (miRNAs) play essential roles in several physiological and pathological processes, including tumor metastasis. Metastasis is associated with poor prognosis in renal carcinoma patients and almost 20-30% of patients present with distant metastasis at the time of diagnosis. The aim of the present study was to investigate the possible roles of miR-200c in regulating metastasis and to identify its target genes in renal cell carcinoma (RCC). Among the miRNAs downregulated in our tissue specimen microarray, miR-200c was downregulated significantly. Functional assays demonstrated that restoration of miR-200c significantly inhibited the migration and invasion of SN12-PM6 and 786-0 cells in vitro. Genome-wide gene expression analysis and TargetScan database studies showed that ZEB1, which has been shown to promote tumor invasion and migration through E-cadherin gene silencing, is a promising candidate target gene of miR‑200c. Overexpression of miR-200c in SN12-PM6 and 786-0 cells was concurrent with downregulation of ZEB1 and upregulation of E-cadherin mRNA and protein. In addition, miR-200c affected the protein expression of p-Akt and Akt. Thus, our study demonstrated that miR-200c decreases the metastatic ability of renal carcinoma cells by upregulating E-cadherin through ZEB1 and that modulating the expression of miR-200c could influence Akt protein levels. We therefore concluded that there is an Akt-miR-200c-E-cadherin axis in the epithelial-to-mesenchymal transition process in RCC.
authors.affiliation: Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, PR China.
authors.forename: Xuegang
authors.initials: X
authors.lastname: Wang
authors.forename: Xuanyu
authors.initials: X
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Wang
authors.forename: Pei
authors.initials: P
authors.lastname: Xiao
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Weiwei
authors.initials: W
authors.lastname: Hang
authors.forename: Anming
authors.initials: A
authors.lastname: Ruan
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D015820:Cadherins; D018398:Homeodomain Proteins; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D051057:Proto-Oncogene Proteins c-akt