title: Re-expression of miR-199a suppresses renal cancer cell proliferation and survival by targeting GSK-3β.
abstract: Recently, we have identified GSK-3 as a new therapeutic target in renal cell cancer (RCC). miR-199a could potentially downregulate GSK-3β expression. Here, we found a decreased miR-199a expression in 59% (32 of 54) of RCCs and it was correlated with higher tumor stage (p < 0.05) and nuclear overexpression of GSK-3β (p < 0.05). We show that re-expression of miR-199a downregulates GSK-3β and suppresses cancer cell growth. Our results demonstrate low miR-199a expression as a feature of advanced RCCs, identify miR-199a as a negative regulator of GSK-3β, and suggest re-expression of pre-miR-199a as a new potential treatment of RCC.
authors.affiliation: Laboratory of Molecular Oncology, Department of Urology, Yamagata University School of Medicine, Iida-nishi 2-2-2, Yamagata 990-9585, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Tsukigi
authors.forename: Vladimir
authors.initials: V
authors.lastname: Bilim
authors.forename: Kaori
authors.initials: K
authors.lastname: Yuuki
authors.forename: Andrey
authors.initials: A
authors.lastname: Ugolkov
authors.forename: Sei
authors.initials: S
authors.lastname: Naito
authors.forename: Akira
authors.initials: A
authors.lastname: Nagaoka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kato
authors.forename: Teiichi
authors.initials: T
authors.lastname: Motoyama
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tomita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged
chemical_list: D035683:MicroRNAs; C531408:mirn199 microRNA, human; D038362:Glycogen Synthase Kinase 3