title: RNAi-mediated knockdown of the CLN3 gene inhibits proliferation and promotes apoptosis in drug-resistant ovarian cancer cells.
abstract: CLN3 is a recently identified anti-apoptotic gene, which has been demonstrated to be highly expressed in a diverse range of cancer cell lines, including ovarian cancer. In the present study, RNA interference, mediated by a lentivirus expressing CLN3 short hairpin RNA (shRNA) was utilized to knockdown the expression of CLN3 in the A2780 human ovarian cancer cell line, and its cisplatin‑resistant and carboplatin‑resistant sublines, A2780/DDP and A2780/CBP cells. It was revealed that the mRNA and protein expression levels of CLN3 were significantly reduced in the CLN3‑specific shRNA‑transduced cells, compared with the untransduced and control shRNA‑transduced cells. In addition, specific knockdown of CLN3 in these cells inhibited cell proliferation and led to cell cycle arrest at the G0/G1 phase, with eventual apoptosis. CLN3 knockdown caused increases in the levels of Bax, FAX, cleaved‑caspase 3, cleaved‑caspase 8 and cleaved‑RARP, but decreased the level of Bcl‑2. Finally, it was observed that CLN3 depletion markedly reduced the half maximum inhibitory concentration in the A2780/DDP and A2780/CBP cells. Taken together, these data suggested that CLN3 is involved in tumorigenesis and drug resistance in ovarian cancer, and may serve as a promising therapeutic target for its treatment.
authors: Department of Gynaecology and Obstetrics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors: Dongwei
authors: D
authors: Mao
authors: Department of Gynaecology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150037, P.R. China.
authors: Jianhua
authors: J
authors: Che
authors: Department of Gynaecology and Obstetrics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors: Shiyu
authors: S
authors: Han
authors: Department of Gynaecology and Obstetrics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors: Honghui
authors: H
authors: Zhao
authors: Department of Gynaecology and Obstetrics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors: Yumei
authors: Y
authors: Zhu
authors: Department of Gynaecology and Obstetrics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
authors: Hong
authors: H
authors: Zhu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016190:Carboplatin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D018832:Molecular Chaperones / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C105199:CLN3 protein, human; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D034741:RNA, Small Interfering; D016190:Carboplatin; D002945:Cisplatin