E2F-1 targets miR-519d to regulate the expression of the ras homolog gene family member C

// Xiu-Bo Sang 1 , Zhi-Hong Zong 2 , Li-Li Wang 1 , Dan-Dan Wu 1 , Shuo Chen 1 , Bo-Liang Liu 1 , Yang Zhao 1 1 Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P. R. China 2 Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 110001, P. R. China Correspondence to: Yang Zhao, email: yida.zhaoyang@163.com Keywords: ovarian carcinoma, E2F1, microRNA-519d, RhoC, tumorigenesis and progression Received: May 20, 2016 Accepted: January 16, 2017 Published: January 27, 2017 ABSTRACT E2F1 (E2F transcription factor 1) can act as a tumor suppressor or oncogene. We report the molecular mechanism of E2F1 in ovarian carcinoma tumorigenesis and progression. E2F1 expression levels in ovarian carcinoma tissue were examined by immunohistochemistry. After E2F1 plasmid transfection and E2F1-microRNA-519d (miR-519d)/si-RhoC (Ras homolog gene family member C) co-transfection, ovarian cancer cell phenotypes and the related molecules were examined in vitro and in vivo . E2F1 was overexpressed in type I and type II ovarian carcinoma as compared to normal ovary tissues and normal fallopian tube tissues, respectively. E2F1 overexpression promoted cell proliferation, G1–S progression, survival, migration, and invasion in vitro ; miR-519d or siRhoC co-transfection reversed E2F1 oncogenic effects. E2F1 overexpression promoted tumor growth in vivo ; miR-519d overexpression inhibited it. E2F1 overexpression increased RhoC, Bcl-2, cyclin D1, survivin, MMP2 (matrix metalloproteinase 2), MMP9, STAT3 (signal transducer and activator of transcription 3), and HuR (ELAV-like RNA-binding protein 1) expression; miR-519d overexpression decreased their expression. E2F1 downregulated miR-519d directly and miR-519d downregulated RhoC directly. Conversely, miR-519d directly downregulated E2F1, There is a direct repressive regulatory loop between E2F1 and miR-519d. We provide evidence that E2F1/miR-519d/RhoC is a promising signaling pathway for diagnosing and treating ovarian carcinoma.