L Li1, Q-H Xu, Y-H Dong, G-X Li, L Yang, L-W Wang, H-Y Li. 1. Department of Obstetrics and Gynecology, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. Hongyulili@outlook.com.
Abstract
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.
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, humanovarian 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.
Authors: Cameron M Armstrong; Chengfei Liu; Wei Lou; Alan P Lombard; Christopher P Evans; Allen C Gao Journal: Prostate Date: 2017-06 Impact factor: 4.104
Authors: Johannes Neu; Piotr Jan Dziunycz; Andreas Dzung; Karine Lefort; Martin Falke; Rémy Denzler; Sandra Nicole Freiberger; Guergana Iotzova-Weiss; Aleksandar Kuzmanov; Mitchell Paul Levesque; Gian-Paolo Dotto; Günther Franz L Hofbauer Journal: PLoS One Date: 2017-09-20 Impact factor: 3.240