Involvement of miR-200a in chemosensitivity regulation of ovarian cancer

Abstract

To explore the role of miR-200a in chemosensitivity regulation of ovarian cancer. Firstly miR-200a was up-regulated in ovarian cancer cell lines (SKOV-3 and ES-2) by lentiviral vector. Then the effects of miR-200a on cytotoxicity of paclitaxel and cisplatin were investigated by methyl thiazolyl tetrazolium (MTT). Furthermore miR-200a regulation of chemoresistance associated with ATP-binding cassette (ABC) family genes expression was detected by quantitative real-time polymerase chain reaction (PCR) and Western blot. Finally the interaction between miR-200a and ABCG2 mRNA 3'untranslated region (3'-UTR) was verified by dual-luciferase reporter assay. An over-expression of miR-200a were successfully achieved in SKOV-3 and ES-2 cells. MiR-200a enhanced the chemosensitivity of SKOV-3 and ES-2 to paclitaxel, but not to cisplatin. Chemoresistance associated ABC family (ABCB3, ABCC1, ABCC2, ABCC3, ABCG2) were down-regulated by miR-200a at several levels. However, the direct interaction between miR-200a and the 3'-UTR of ABCG2 mRNA was not found. An over-expression of miR-200a may increase chemosensitivity to paclitaxel in ovarian cancer cells through negatively regulated chemoresistance associated ABC family. However, no direct action on 3'-UTR of ABCG2 was not found after its down-regulation by miR-200a.