title: ClC-3 Chloride Channel Proteins Regulate the Cell Cycle by Up-regulating cyclin D1-CDK4/6 through Suppressing p21/p27 Expression in Nasopharyngeal Carcinoma Cells.
abstract: It was shown in this study that knockdown of ClC-3 expression by ClC-3 siRNA prevented the activation of hypotonicity-induced chloride currents, and arrested cells at the G0/G1 phase in nasopharyngeal carcinoma CNE-2Z cells. Reconstitution of ClC-3 expression with ClC-3 expression plasmids could rescue the cells from the cell cycle arrest caused by ClC-3 siRNA treatments. Transfection of cells with ClC-3 siRNA decreased the expression of cyclin D1, cyclin dependent kinase 4 and 6, and increased the expression of cyclin dependent kinase inhibitors (CDKIs), p21 and p27. Pretreatments of cells with p21 and p27 siRNAs depleted the inhibitory effects of ClC-3 siRNA on the expression of CDK4 and CDK6, but not on that of cyclin D1, indicating the requirement of p21 and p27 for the inhibitory effects of ClC-3 siRNA on CDK4 and CDK6 expression. ClC-3 siRNA inhibited cells to progress from the G1 phase to the S phase, but pretreatments of cells with p21 and p27 siRNAs abolished the inhibitory effects of ClC-3 siRNA on the cell cycle progress. Our data suggest that ClC-3 may regulate cell cycle transition between G0/G1 and S phases by up-regulation of the expression of CDK4 and CDK6 through suppression of p21 and p27 expression.
authors.affiliation: Department of Physiology, Guangdong Pharmaceutical University, Guangzhou, China.|Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Ye
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Zhouyi
authors.initials: Z
authors.lastname: Lai
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Physiology, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Mao
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: Tim
authors.initials: T
authors.lastname: Jacob
authors.affiliation: College of Pharmacy, Jinan University, Guangzhou, China.
authors.forename: Wencai
authors.initials: W
authors.lastname: Ye
authors.affiliation: Department of Physiology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000235:genetics*; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000235:genetics*; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors / Q000235:genetics*; D051361:Cyclin-Dependent Kinase 6 / Q000037:antagonists & inhibitors / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics; D016196:S Phase / Q000235:genetics; D015533:Transcriptional Activation / Q000235:genetics
chemical_list: C530104:CCND1 protein, human; D018118:Chloride Channels; C115376:ClC-3 channel; D050759:Cyclin-Dependent Kinase Inhibitor p21; D034741:RNA, Small Interfering; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6