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

// Bo-Liang Liu 1 , Kai-Xuan Sun 1 , Zhi-Hong Zong 2 , Shuo Chen 1 , Yang Zhao 1 1 Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China 2 Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 100013, China Correspondence to: Yang Zhao, e-mail: yida.zhaoyang@163.com Keywords: endometrial carcinoma, microRNA-372, RhoC, tumorigenesis, progression Received: July 23, 2015 Accepted: November 16, 2015 Published: December 09, 2015 ABSTRACT 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.