E2F-1 targets miR-519d to regulate the expression of the ras homolog gene family member C.
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.
Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P. R. China.
Xiu-Bo
XB
Sang
Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 110001, P. R. China.
Zhi-Hong
ZH
Zong
Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P. R. China.
Li-Li
LL
Wang
Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P. R. China.
Dan-Dan
DD
Wu
Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P. R. China.
Shuo
S
Chen
Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P. R. China.
Bo-Liang
BL
Liu
Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, P. R. China.
Yang
Y
Zhao
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D050687:E2F1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous; D055815:Young Adult; D020741:rho GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000075024:rhoC GTP-Binding Protein
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C546194:MIRN519 microRNA, human; D035683:MicroRNAs; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D000075024:rhoC GTP-Binding Protein
E2F1; RhoC; microRNA-519d; ovarian carcinoma; tumorigenesis and progression