Juanni Li1, Long Li1, Zexia Li2, Guanghui Gong1, Puxiang Chen3, Hailing Liu1, Junpu Wang1, Ying Liu1, Xiaoying Wu4. 1. Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Pathology, School of Basic Medical Science, Central South University, Changsha 410013, China. 2. Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China; Microarray Core Facility, University of Texas Southwestern Medical Center, 75070, USA. 3. Department of Gynecology and Obstetrics, Second Xiangya Hospital, Central South University, Changsha 410011, China. 4. Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China; Department of Pathology, School of Basic Medical Science, Central South University, Changsha 410013, China. Electronic address: xyw2007@csu.edu.cn.
Abstract
OBJECTIVE: Our objective was to investigate a miRNA pathway that acts downstream of VEGF-induced invasion of ovarian cancer cells. METHOD: We used two paired high and low metastatic serous ovarian cancer cells to demonstrate the role of miR-205 in VEGF-induced invasion of ovarian cancer cells and to investigate the gene targets of miR-205. RESULTS: Our previous comparative proteomics studies showed that VEGF decreased the expression of Ezrin and Lamin A/C, and this result was validated in the present study using qPCR and Western blotting. Then we found that VEGF enhanced the invasiveness of and inhibited apoptosis in ovarian cancer cells as assessed by transwell invasion assays and Annexin V-FITC immunostaining, respectively. VEGFR was also expressed in ovarian cancer cells, as assessed by immunocytochemical staining. Furthermore, using the dual-luciferase report assay system, we demonstrated that miR-205 targeted Ezrin and Lamin A/C. MiR-205 was up-regulated in ovarian cancer cells exposed to VEGF, as determined by miRNA microarray analysis and verified by qPCR. MiR-205 promoted the invasion and proliferation of ovarian cancer cells. CONCLUSION: Our data reveal a new potential pathway in which VEGF promotes the invasion of ovarian cancer cells, partially via the down-regulation of Ezrin and Lamin A/C caused by increased expression of miR-205.
OBJECTIVE: Our objective was to investigate a miRNA pathway that acts downstream of VEGF-induced invasion of ovarian cancer cells. METHOD: We used two paired high and low metastatic serous ovarian cancer cells to demonstrate the role of miR-205 in VEGF-induced invasion of ovarian cancer cells and to investigate the gene targets of miR-205. RESULTS: Our previous comparative proteomics studies showed that VEGF decreased the expression of Ezrin and Lamin A/C, and this result was validated in the present study using qPCR and Western blotting. Then we found that VEGF enhanced the invasiveness of and inhibited apoptosis in ovarian cancer cells as assessed by transwell invasion assays and Annexin V-FITC immunostaining, respectively. VEGFR was also expressed in ovarian cancer cells, as assessed by immunocytochemical staining. Furthermore, using the dual-luciferase report assay system, we demonstrated that miR-205 targeted Ezrin and Lamin A/C. MiR-205 was up-regulated in ovarian cancer cells exposed to VEGF, as determined by miRNA microarray analysis and verified by qPCR. MiR-205 promoted the invasion and proliferation of ovarian cancer cells. CONCLUSION: Our data reveal a new potential pathway in which VEGF promotes the invasion of ovarian cancer cells, partially via the down-regulation of Ezrin and Lamin A/C caused by increased expression of miR-205.
Authors: Stefan Riwaldt; Johann Bauer; Markus Wehland; Lasse Slumstrup; Sascha Kopp; Elisabeth Warnke; Anita Dittrich; Nils E Magnusson; Jessica Pietsch; Thomas J Corydon; Manfred Infanger; Daniela Grimm Journal: Int J Mol Sci Date: 2016-04-08 Impact factor: 5.923