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 nuc...

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Bibliographic Details
Published in:Cancer letters 2012-02, Vol.315 (2), p.189-197
Main Authors: Tsukigi, Masaaki, Bilim, Vladimir, Yuuki, Kaori, Ugolkov, Andrey, Naito, Sei, Nagaoka, Akira, Kato, Tomoyuki, Motoyama, Teiichi, Tomita, Yoshihiko
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Apoptosis
Blotting, Western
Carcinoma, Renal Cell - pathology
Cell Line, Tumor
Cell Proliferation
Cell Survival
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Glycogen Synthase Kinase 3 - metabolism
Glycogen synthase kinase-3β
Hematology, Oncology and Palliative Medicine
Humans
Immunohistochemistry
Male
MicroRNAs - metabolism
Middle Aged
miR-199
Renal cell carcinoma
Targeted therapy
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Summary: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.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2011.10.008