title: Loss of miR-200c up-regulates CYP1B1 and confers docetaxel resistance in renal cell carcinoma.
abstract: Despite high protein expression and enzymatic activity of cytochrome P450 1B1 (CYP1B1) in renal cell cancer (RCC), its functional significance has not been elucidated. Here we explored the functional role and regulatory mechanism of CYP1B1 in RCC. Reduction of CYP1B1 levels fail to prevent in vitro tumorigenicity such as proliferation, apoptosis, and cell cycle progression of RCC cells. Moreover, the expression levels are not associated with tumor type, stage, Fuhrman grade and 5-year survival probability after surgery. Instead, alteration of CYP1B1 expression regulates the chemosensitivity of RCC cells to docetaxel suggesting its critical contribution to the chemoresistance. Additionally, miR-200c, which is significantly down-regulated in RCC regulates CYP1B1 expression and activity. An inverse association was also observed between the expression levels of miR-200c and CYP1B1 protein in RCC tissues. Finally, alteration of miR-200c levels affects the chemosensitivity of RCC cells. Restoration of docetaxel resistance by exogenous expression of CYP1B1 in miR-200c-over-expressing cells indicates that CYP1B1 is a functional target of miR-200c. These results suggest that CYP1B1 up-regulation mediated by low miR-200c is one of the mechanisms underlying resistance of RCC cells to docetaxel. Therefore, expression of CYP1B1 and miR-200c in RCC may be useful as a prediction for docetaxel response.
authors: Department of Surgery and Division of Urology, Veterans Affairs Medical Center, San Francisco, California, United States of America.|Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea.
authors: Inik
authors: I
authors: Chang
authors: Department of Surgery and Division of Urology, Veterans Affairs Medical Center, San Francisco, California, United States of America.|Department of Urology, University of California, San Francisco, California, United States of America.
authors: Yozo
authors: Y
authors: Mitsui
authors: Department of Surgery and Division of Urology, Veterans Affairs Medical Center, San Francisco, California, United States of America.|Department of Urology, University of California, San Francisco, California, United States of America.
authors: Shinichiro
authors: S
authors: Fukuhara
authors: Department of Surgery and Division of Urology, Veterans Affairs Medical Center, San Francisco, California, United States of America.
authors: Ankurpreet
authors: A
authors: Gill
authors: Department of Surgery and Division of Urology, Veterans Affairs Medical Center, San Francisco, California, United States of America.
authors: Darryn K
authors: DK
authors: Wong
authors: Department of Surgery and Division of Urology, Veterans Affairs Medical Center, San Francisco, California, United States of America.|Department of Urology, University of California, San Francisco, California, United States of America.
authors: Soichiro
authors: S
authors: Yamamura
authors: Department of Surgery and Division of Urology, Veterans Affairs Medical Center, San Francisco, California, United States of America.
authors: Varahram
authors: V
authors: Shahryari
authors: Department of Pathology, Veterans Affairs Medical Center and University of California, San Francisco, California, United States of America.
authors: Z Laura
authors: ZL
authors: Tabatabai
authors: Department of Surgery and Division of Urology, Veterans Affairs Medical Center, San Francisco, California, United States of America.|Department of Urology, University of California, San Francisco, California, United States of America.
authors: Rajvir
authors: R
authors: Dahiya
authors: Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea.
authors: Dong Min
authors: DM
authors: Shin
authors: Department of Surgery and Division of Urology, Veterans Affairs Medical Center, San Francisco, California, United States of America.|Department of Urology, University of California, San Francisco, California, United States of America.
authors: Yuichiro
authors: Y
authors: Tanaka
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1 / Q000235:genetics / Q000378:metabolism*; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D043823:Taxoids / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D043823:Taxoids; D000077143:Docetaxel; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1
keywords: CYP1B1; chemotherapy; docetaxel; miR-200c; renal cell carcinoma