title: Involvement of microRNA-93, a new regulator of PTEN/Akt signaling pathway, in regulation of chemotherapeutic drug cisplatin chemosensitivity in ovarian cancer cells.
abstract: The mechanisms underlying ovarian cancer cell resistance to cisplatin (CDDP) are not fully understood. MicroRNAs (miRNAs) play important roles in tumorigenesis and drug resistance. In this paper, we utilized microRNA array and real-time PCR to show that miR-93 is significantly up-regulated in cisplatin-resistant ovarian cancer cells. In vitro assays show that over-expression and knock-down of miR-93 regulate apoptotic activity, and thereby cisplatin chemosensitivity, in ovarian cells. Furthermore, we found that miR-93 can directly target PTEN, and participates in the regulation of the AKT signaling pathway. MiR-93 inversely correlates with PTEN expression in CDDP-resistant and sensitive human ovarian cancer tissues. These results may have implications for therapeutic strategies aiming to overcome ovarian cancer cell resistance to cisplatin.
authors.affiliation: Department of Gynecology Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Fu
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Quan
authors.initials: Q
authors.lastname: Hao
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000473:pathology*; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C543350:MIRN93 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; D002945:Cisplatin