title: MTA1 promotes cell proliferation via DNA damage repair in epithelial ovarian cancer.
abstract: We examined whether metastasis-associated gene 1 (MTA1) promotes cell proliferation via DNA damage repair in ovarian cancer. MTA1 was successfully down-regulated using small interfering RNA in the epithelial ovarian cancer cell lines SKOV-3 and OVCAR-3. Cell growth was evaluated through MTT and colony formation assays. Fluorescence-activated cell sorting analysis was used to evaluate the distribution of cells in the cell cycle, and cytotoxicity assays were performed to study cell sensitivity to cisplatin. A neutral comet assay was used to measure levels of ionizing radiation-induced DNA damage in SKOV-3 cells, and Western blot analyses were carried out to examine the expression of key proteins involved in DNA damage repair pathways. MTA1 knockdown markedly inhibited cell growth and led to S phase cell cycle arrest. In addition, MTA1 depletion conferred sensitivity of ovarian cancer cells to cisplatin. Moreover, MTA1 depletion increased the level of ionizing radiation-induced DNA damage and caused irreparable damage, which was illustrated by a remarkable increase and persistent existence of a comet tail as well as protein expression levels of γH2AX, pRPA, and pChk1, all of which play critical roles in DNA repair. Thus, MTA1 promotes the proliferation of epithelial ovarian cancer cells by enhancing DNA repair.
authors.affiliation: Department of Laboratory Medicine, Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Q Y
authors.initials: QY
authors.lastname: Yang
authors.affiliation: Central Laboratory, Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: J H
authors.initials: JH
authors.lastname: Li
authors.affiliation: Department of Gynecology and Obstetrics, Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Q Y
authors.initials: QY
authors.lastname: Wang
authors.affiliation: Department of Gynecology and Obstetrics, Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Gynecology and Obstetrics, Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: J L
authors.initials: JL
authors.lastname: Qin
authors.affiliation: Department of Gynecology and Obstetrics, Tenth People's Hospital of Tongji University, Shanghai, China.
authors.forename: J J
authors.initials: JJ
authors.lastname: Cheng
authors.affiliation: Department of Gynecology and Obstetrics, Tenth People's Hospital of Tongji University, Shanghai, China Laboratorypan@aliyun.com.
authors.forename: J
authors.initials: J
authors.lastname: Qiu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000077216:Carcinoma, Ovarian Epithelial; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004273:DNA, Neoplasm / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000494:pharmacology*; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D015534:Trans-Activators
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; C089320:MTA1 protein, human; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D015534:Trans-Activators; D006655:Histone Deacetylases; D002945:Cisplatin