The role of miR-205 in the VEGF-mediated promotion of human ovarian cancer cell invasion

Juanni Li; Long Li; Zexia Li; Guanghui Gong; Puxiang Chen; Hailing Liu; Junpu Wang; Ying Liu; Xiaoying Wu

doi:10.1016/j.ygyno.2015.01.531

The role of miR-205 in the VEGF-mediated promotion of human ovarian cancer cell invasion

Gynecol Oncol. 2015 Apr;137(1):125-33. doi: 10.1016/j.ygyno.2015.01.531. Epub 2015 Jan 15.

Authors

Juanni Li¹, Long Li¹, Zexia Li², Guanghui Gong¹, Puxiang Chen³, Hailing Liu¹, Junpu Wang¹, Ying Liu¹, Xiaoying Wu⁴

Affiliations

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.

PMID: 25597268
DOI: 10.1016/j.ygyno.2015.01.531

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.

Keywords: Ezrin; Invasion; Lamin A/C; MiR-205; Ovarian cancer; VEGF.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / physiology
Carcinoma, Ovarian Epithelial
Cell Line, Tumor
Cytoskeletal Proteins / biosynthesis
Cytoskeletal Proteins / metabolism
Down-Regulation
Female
Humans
Lamin Type A / biosynthesis
Lamin Type A / metabolism
MicroRNAs / biosynthesis
MicroRNAs / genetics
MicroRNAs / metabolism*
Neoplasm Invasiveness
Neoplasms, Glandular and Epithelial / genetics
Neoplasms, Glandular and Epithelial / metabolism*
Neoplasms, Glandular and Epithelial / pathology*
Ovarian Neoplasms / genetics
Ovarian Neoplasms / metabolism*
Ovarian Neoplasms / pathology*
Transfection
Vascular Endothelial Growth Factor A / biosynthesis
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / metabolism*
Vascular Endothelial Growth Factor Receptor-1 / metabolism

Substances

Cytoskeletal Proteins
LMNA protein, human
Lamin Type A
MIRN205 microRNA, human
MicroRNAs
VEGFA protein, human
Vascular Endothelial Growth Factor A
ezrin
FLT1 protein, human
Vascular Endothelial Growth Factor Receptor-1