title: Knockdown of regulator of cullins-1 (ROC1) expression induces bladder cancer cell cycle arrest at the G2 phase and senescence.
abstract: Regulator of Cullins-1 (ROC1) is a key subunit in the Cullin-RING ligase (CRL) protein complex. Overexpression of ROC1 protein is associated with tumor progression and poor prognosis of non-muscle invasive bladder transitional cell carcinoma (NMIBC). This study was designed to assess the effects of ROC1 knockdown in bladder cancer cells and to determine the potential mechanisms involved. A total of 112 bladder cancer tissue specimens were recruited for immunohistochemical analyses of ROC1 overexpression. Bladder cancer cell lines were used to knockdown ROC1 expression using ROC1 siRNA. Our data showed that ROC1 knockdown remarkably inhibited bladder cancer cell growth, arrested cells at the G2 phase of the cell cycle, and induced the p53-dependent cell senescence. Molecularly, G2 arrest was associated with upregulation of p21, p27, cyclin B1, and Cdc2 proteins. ROC1 knockdown induced-senescence functioned through p53/p21 pathway. Knockdown of p21 expression partially rescued ROC1 knockdown-induced growth inhibition in cancer cells. Furthermore, nude mouse xenograft analyses confirmed these in vitro data. In conclusion, data from the current study indicate that ROC1 plays an essential role in bladder cancer progression and could serve as a novel anticancer target for bladder transitional cell carcinoma (BTCC).
authors.affiliation: Department of Urology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Qu
authors.forename: Zhengdong
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yigang
authors.initials: Y
authors.lastname: Zeng
authors.forename: Jie
authors.initials: J
authors.lastname: Fan
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Guo
authors.forename: Jianxin
authors.initials: J
authors.lastname: Qiu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000502:physiology*; D002681:China; D003114:Colony-Forming Units Assay; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D059565:G2 Phase Cell Cycle Checkpoints / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D001616:beta-Galactosidase
chemical_list: C493956:CDKN1A protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D017931:DNA Primers; C479529:RBX1 protein, human; D034741:RNA, Small Interfering; D001616:beta-Galactosidase