Overexpression of MEF2D contributes to oncogenic malignancy and chemotherapeutic resistance in ovarian carcinoma

American Journal of Cancer Research

Shuhua Zhou¹  Xiaoshan Chai²  Xiaoxue Li³  Yongjing Zhang⁴ 

[1] Department of Chemistry and Biological Sciences, University of Southern California, 1050 Childs Way, RRI 204c, Los Angeles 90089, CA, USA;Department of Gynecology Oncology, The Hunan Province Cancer Hospital, Changsha 410013, China;Department of Obstetrics and Gynecology, The Second Xiang Ya Hospital of Central South University, Changsha 410011, China;Department of Pathology, The Second Xiang Ya Hospital of Central South University, Changsha 410011, China

关键词: Ovarian cancer (OC);    MEF2D;    cisplatin-resistant;    IKBKE;    HPSE;   

DOI  :  

学科分类：肿瘤学

来源: e-Century Publishing Corporation

【 摘 要 】

The transcription factor MEF2 promotes survival in various cell types and a number of studies indicate that abnormal regulation of MEF2 is linked to oncogenicity in several carcinomas. We have found that MEF2D, a member of the MEF2 family, is upregulated in Ovarian Cancer (OC). Immunohistochemistry analysis of tumor sections of 402 OC patients revealed that MEF2D is significantly elevated at the protein level. We have also found that the expression level of MEF2D is associated with cisplatin-resistance and poor prognosis by a retrospective analysis. Furthermore, Downregulation of MEF2D by siRNA reduces proliferation and invasiveness of OC cells SKOV3 and OVCAR3, induces apoptosis in vitro, and abolishes OVCAR3 tumorigenicity in xenograft model. Mechanistic study via ChIP analysis identified two of MEF2D-targeted genes, HPSE and IKBKE, which are associated with tumor invasion and chemotherapy-resistance, in accord with MEF2D expression in OC. Remarkably, knock-down of MEF2D invariably lead to the downregulation of IKBKE and reversed cisplatin (DDP)-resistance in cisplatin-resistant cells SKOV3-DDP. Our results suggest that MEF2D promotes malignant biological behaviors and cisplatin-resistance in OC and establish MEF2D as a new therapeutic target in OC treatment.

【 授权许可】

CC BY-NC