title: Epithelial-mesenchymal transition-related microRNA-200s regulate molecular targets and pathways in renal cell carcinoma.
abstract: Our recent studies of microRNA (miRNA) expression signatures demonstrated that the epithelial-mesenchymal transition (EMT)-related microRNA-200 family (miR-200s: miR-200a/b/c, miR-141 and miR-429) were significantly downregulated in renal cell carcinoma (RCC) and putative tumor-suppressive miRNAs in RCC. In this study, our aim was to investigate the functional significance of the miR-200s in cancer cells and to identify novel miR-200s-regulated molecular targets and pathways in RCC. Expression levels of all the miR-200s members were significantly downregulated in human RCC tissues compared with normal renal tissues. Restoration of mature miR-200s in RCC cell line resulted in significant inhibition of cell proliferation and migration, suggesting that miR-200s function as tumor suppressors in RCC. Furthermore, we utilized gene expression analysis and in silico database analysis to identify miR-200s-regulated molecular targets and pathways in RCC. The miR-200s was categorized into two groups, according to their seed sequences, miR-200b/c/429 and miR-200a/141. Our data demonstrated that the 'Focal adhesion' and 'ErbB signaling' pathways were significantly regulated by miR-200b/c/429 and miR-200a/141, respectively. The identification of novel tumor-suppressive miR-200s-regulated molecular targets and pathways has provided new insights into RCC oncogenesis and metastasis.
authors: Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
authors: Hirofumi
authors: H
authors: Yoshino
authors: Hideki
authors: H
authors: Enokida
authors: Toshihiko
authors: T
authors: Itesako
authors: Shuichi
authors: S
authors: Tatarano
authors: Takashi
authors: T
authors: Kinoshita
authors: Miki
authors: M
authors: Fuse
authors: Satoko
authors: S
authors: Kojima
authors: Masayuki
authors: M
authors: Nakagawa
authors: Naohiko
authors: N
authors: Seki
mesh_terms: D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002877:Chromosomes, Human / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics*; D014162:Transfection
chemical_list: C533895:MIRN141 microRNA, human; C533896:MIRN200 microRNA, human; C546363:MIRN429 microRNA, human; D035683:MicroRNAs