Connexin 26 is Down-Regulated by KDM5B in the Progression of Bladder Cancer.docVIP

Int. J. Mol. Sci. 2013, 14, 7866-7879; doi:10.3390/ijmOPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Article Connexin 26 is Down-Regulated by KDM5B in the Progression of Bladder Cancer Xin Li 1,2, Yongping Su *, Jinhong Pan *, Zhansong Zhou , Bo Song , Enqing Xiong and 2, 1, 1 1 1 Zhiwen Chen 1 1 Urologic Institute of PLA, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; E-Mails: xinlicq@ (X.L.); zhansongzhoucq@ (Z.Z.); bosongcq@ (B.S.); enqingxiongcq@ (E.X.); zhiwenchencq@ (Z.C.) 2 State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Third Military Medical University, Chongqing 400038, China * Authors to whom correspondence should be addressed; E-Mails: yongpingsucq@163.com (Y.S.); jinhongpancq@ (J.P.); Tel.: +86-23-6876-5816 (J.P.); Fax: +86-23-6876-5817 (J.P.). Received: 4 February 2013; in revised form: 20 February 2013 / Accepted: 6 March 2013 / Published: 11 April 2013 Abstract: Connexin 26 (Cx26) expression is down-regulated and KDM5B (H3K4 demethylase) is up-regulated in the progression of bladder cancer, suggesting that Cx26 expression may be down-regulated by KDM5B in bladder cancer. To test the hypothesis, the HT1376 and T24 human bladder carcinoma cells were transfected with the plasmids pcDNA3.1-KDM5B, and caused the down-regulation of Cx26 expression. In contrast, the HT1376 and T24 cells transfected with the plasmids pTZU6+1-shRNA-KDM5B1 and pTZU6+1-shRNA-KDM5B2 caused the up-regulation of Cx26 expression. Immunohistochemistry and Spearman’s rank correlation analysis showed that the immunohistochemical expression of KDM5B and Cx26 was inversely related in bladder carcinoma tissues but no relationship in benign tissues. Taken together, these results indicate that KDM5B represses Cx26 expression in the bladder cancer develop