OBJECTIVE: Elevated miR-181a is associated with the transition of ovarian tissues from normal into a cancerous state. However, its regulative effect on multidrug resistance (MDR) of ovarian cancer is not quite clear. Therefore, this study aimed to investigate its regulative effects on epithelial-to-mesenchymal transition (EMT) and MDR in ovarian cancer.
MATERIALS AND METHODS: The expression profile of miR-181a in normal and ovarian cancer tissues was firstly quantified using qRT-PCR analysis. Then, human ovarian cancer cell line SKOV3 were transfected for miR-181a overexpression and the paclitaxel-resistant variant SKOV3/PTX cells were transfected for miR-181a knockdown. The effect of miR-181a overexpression/knockdown on EMT and PTX sensitivity were studied.
RESULTS: MiR-181a level in chemoresistant (CR) cancer tissues were significantly higher than in chemosensitive (CS) cancer tissues and in normal tissue. SKOV3/PTX cells had significantly higher expression of miR-181a and N-cadherin than SKOV3 cells. SKOV3 cells had decreased E-cadherin expression and increased N-cadherin expression after enforced miR-181a expression, while SKOV3/PTX cells had increased E-cadherin expression and decreased N-cadherin expression after miR-181a knockdown. SKOV3 cells had increased P-gp expression after enforced miR-181a expression. Following MTT assay and flow cytometry analysis both confirmed that miR-181a overexpression decreased the PTX sensitivity of SKOV3 cells and while miR-181a inhibition increased the sensitivity of SKOV3/PTX cells.
CONCLUSIONS: MiR-181a is an important oncomiR significantly increased in chemoresistant ovarian cancer. Its upregulation is associated with increased level of EMT and decreased cell apoptosis induced by PTX treatment.Free PDF Download
To cite this article
L. Li, Q.-H. Xu, Y.-H. Dong, G.-X. Li, L. Yang, L.-W. Wang, H.-Y. Li
MiR-181a upregulation is associated with epithelial-to-mesenchymal transition (EMT) and multidrug resistance (MDR) of ovarian cancer cells
Eur Rev Med Pharmacol Sci
Vol. 20 - N. 10