Mir-200c Inhibits Hotair Expression Resulting In The Decrease Of Chemoresistance In Ovarian Cancer Stem Cells

In this study, we investigated whether miR-200c overexpression would increase the sensitivity of epithelial ovarian cancer (EOC) stem cells (CSCs) to chemotherapy drugs through down-regulation of lncRNA HOTAIR. We used a magnetic-activated cell sorting system to isolate the SKOV3 CD44(+)CD117(+)CSCs from the selected human EOC SKOV3 cells that were stably transduced with lentivirus miR-200c. HOTAIR, a direct target of miR-200c, was validated by using the wild-type and the mutant region HOTAIR luciferase reporters. The results showed the overexpression of miR-200c in SKOV3 CD44(+)CD117(+)CSCs significantly decreased the drug resistant to paclitaxel and cisplatin compared with SKOV3 CD44(+) CD117(+) CSCs transduced with the lentivirus-mock or the wild-type of SKOV3 CD44(+) CD117(+)CSCs. Moreover, SKOV3 CD44(+) CD117(+)CSCs with miR-200c overexpression dramatically reduced its metastatic potential from the tumor tissues to the nude mouse lungs in contrast to SKOV3 CD44(+)CD117(+)CSCs without miR-200c overexpression. The direct down-regulation of HOTAIR was miR-200c dependent because luciferase reporter and rescue assay results showed that the putative miR-200c-binding site has the inhibitory effect on HOTAIR expression. Collectively, the increased sensitivity of SKOV3 CD44(+)CD117(+)CSCs to paclitaxel or cisplatin may be modulated by overexpression of miR-200c that directly inhibits HOTAIR expression.