MicroRNA-372 inhibits endometrial carcinoma development by targeting the expression of the Ras homolog gene family member C (RhoC)
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Bo-Liang Liu1, Kai-Xuan Sun1, Zhi-Hong Zong2, Shuo Chen1, Yang Zhao1
1Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang 110001, China
2Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang 100013, China
Yang Zhao, e-mail: [email protected]
Keywords: endometrial carcinoma, microRNA-372, RhoC, tumorigenesis, progression
Received: July 23, 2015 Accepted: November 16, 2015 Published: December 09, 2015
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.
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