Author/Authors :
Kou, Xinxin Department of Gynaecology - Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China , Ding, Hui Department of Gynaecology - Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China , Li, Lei Department of Gynaecology - Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China , Chao, Hongtu Department of Gynaecology - Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China
Abstract :
Purpose. Cisplatin is one of the most effective drugs for treating ovarian carcinoma (OC), which is among the most lethal types of carcinoma. However, the chemoresistance to cisplatin that develops over time leads to a poor clinical outcome for many OCpatients. Therefore, it is necessary to clearly understand the molecular mechanisms of chemoresistance. In this study, weexamined how Hsa-miR-105-1 functions in cisplatin-resistant OC cells.Methods. The levels of Hsa-miR-105-1 expression incisplatin-sensitive and resistant OC cell lines were detected by qRT-PCR. The target gene of Hsa-miR-105-1 was predicted byusing the Target Scan and Starbase databases and verified by the double luciferase reporter gene assay. The target gene ofHsa-miR-105-1 was identified asANXA9, andANXA9expression was evaluated by qRT-PCR, western blotting, andimmunofluorescence. To validate the function of Hsa-miR-105-1 in OC cells, we silenced or overexpressed Hsa-miR-105-1 incisplatin-sensitive or resistant OC cell lines, respectively. Furthermore, the expression levels of several apoptosis-related proteins,including P53, P21, E2F1, Bcl-2, Bax, and caspase-3, were examined by western blot analysis.Results.The levels of Hsa-miR-105-1 expression were abnormally downregulated in cisplatin-resistant OC cells, whileANXA9expression was significantlyupregulated in those cells. Treatment with an Hsa-miR-105-1 inhibitor promoted the expression of ANXA9 mRNA and protein,enhanced the resistance to cisplatin, and attenuated the cell apoptosis induced by cisplatin in cisplatin-sensitive OC cells.Moreover, treatment with Hsa-miR-105-1 mimics inhibitedANXA9expression, which further increased the levels of P53, P21,and Bax expression and decreased the levels of E2F1 and Bcl-2 expression,finally resulting in an increased sensitivity tocisplatin in cisplatin-resistant OC cells.Conclusion. We found that a downregulation of Hsa-miR-105-1 expression enhancedcisplatin-resistance, while an upregulation of Hsa-miR-105-1 restored the sensitivity of OC cells to cisplatin. The Hsa-miR-105-1/ANXA9axis plays an important role in the cisplatin-resistance of OC cells.
