title: Carboplatin-docetaxel-induced activity against ovarian cancer is dependent on up-regulated lncRNA PVT1.
abstract: Ovarian cancer is the fourth most ordinary cause of cancer-related deaths in women. In recent, combination chemotherapy with carboplatin and docetaxel was developed as first-line drug to treat ovarian carcinoma. However, the detailed molecular mechanism, which accounts for the cells to apoptosis induced by administration of carboplatin and docetaxel, was unrecognized. In present study, we provide the mechanistic link between mixture of carboplatin plus docetaxel and its anticancer activity. Primarily, a majority of 30 cancer-related long non-coding RNA (lncRNA) showed differential alteration in carboplatin-docetaxel-treated 3AO cells. Among six up-regulating lncRNAs, we screened out carboplatin-docetaxel-induced lncRNA PVT1 which may be a central downstream target of carboplatin plus docetaxel because expression of PVT1 positively correlates with anticancer action of carboplatin plus docetaxel. Besides, p53 and tissue inhibitor of matrix metalloproteinases-1 (TIMP1) were mediated by lncRNA PVT1, which may explain partially the anticancer activity of lncRNA PVT1. Collectively, we have identified a potential mechanism by which PVT1 regulated by carboplatin plus docetaxel contributes to the carboplatin-docetaxel-induced anticancer action in ovarian cancer. These discoveries also give proof of the potential of PVT1 as significant downstream targets for therapeutic intervention in ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Tangshan Gongren Hospital, Hebei Medical University Tangshan 063000, China.
authors.forename: Enling
authors.initials: E
authors.lastname: Liu
authors.affiliation: Clinical Medical Program 2011, Hebei Medical University China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, Tangshan Gongren Hospital, Hebei Medical University Tangshan 063000, China.
authors.forename: Yuxiu
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D016190:Carboplatin / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D043823:Taxoids / Q000494:pharmacology* / Q000627:therapeutic use; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; C521123:PVT1 long-non-coding RNA, human; D062085:RNA, Long Noncoding; D043823:Taxoids; D019715:Tissue Inhibitor of Metalloproteinase-1; D016159:Tumor Suppressor Protein p53; D000077143:Docetaxel; D016190:Carboplatin
keywords: Ovarian cancer; carboplatin; docetaxel; lncRNA PVT1; p53