MicroRNA-372 inhibits endometrial carcinoma development by targeting the expression of the Ras homolog gene family member C (RhoC)

• Published in: Oncotarget 2016-02, Vol.7 (6), p.6649-6664
• Main Authors: Liu, Bo-Liang, Sun, Kai-Xuan, Zong, Zhi-Hong, Chen, Shuo, Zhao, Yang
• Format: Article
• Language: English
• Subjects: Animals; Carcinogenesis - genetics; Carcinogenesis - metabolism; Cell Line, Tumor; Cell Proliferation - physiology; Disease Progression; Endometrial Neoplasms - genetics; Endometrial Neoplasms - metabolism; Endometrial Neoplasms - pathology; Female; Heterografts; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - administration & dosage; MicroRNAs - biosynthesis; MicroRNAs - genetics; Research Paper; rho GTP-Binding Proteins - biosynthesis; rho GTP-Binding Proteins - genetics; rhoC GTP-Binding Protein; Transfection
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.6544

Here we explore the role of microRNA-372 (miR-372) in tumorigenesis and development of endometrial adenocarcinoma (EC) and analyze the underlying mechanism. We found that miR-372 expression is much lower in EC than normal endometrial specimens. Cell function experiments demonstrated that miR-372 overexpression suppressed cell proliferation, migration, and invasion, and led to a G1 phase arrest and promoted the apoptosis of endometrial carcinoma cells in vitro. The nude mouse xenograft assay demonstrated that miR-372 overexpression suppressed tumor growth. RT-PCR and Western blot assays detected the expression of known targets of miR-372 in other malignant tumors and found Cyclin A1 and Cyclin-dependent Kinase 2 (CDK2) was downregulated by miR-372. Bioinformatic predictions and dual-luciferase reporter assays found that RhoC was a possible target of miR-372. RT-PCR and Western blot assays demonstrated that miR-372 transfection reduced the expression of RhoC, matrix metalloproteinase 2 (MMP2) and MMP9, while it increased the expression of cleaved poly (ADP ribose) polymerase (PARP) and bcl-2-associated X protein (Bax). The cell function experiments that transfected siRNA with RhoC showed the same trend as those which were transfected with miR-372. Taken together, our results demonstrated for the first time that miR-372 suppresses tumorigenesis and the development of EC; RhoC is a new and potentially important therapeutic target.