MicroRNA-93 promotes the tumorigenesis of osteosarcoma by targeting TIMP2. Issue 8 (23rd August 2019)

• Record Type: Journal Article
• Authors: Zhang, Hua; Zhang, Jidong; Meng, Fanrui; Zhu, Hanzhong; Yan, Hongyu; Guo, Yunliang; Zhang, Shandi
• Is Part Of: Bioscience reports. Volume 39:Issue 8(2019)
• Publication Date: 2019-08-23
• Subjects: EMT -- MiR-93 -- osteosarcoma -- TIMP2; Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20191237
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract: Osteosarcoma (OS) is the most frequent primary bone malignancy and affects adolescents and young adults. Recently dysregulation of miRNAs has received more attention because of its extensive role in OS carcinogenesis. This research was designed to verify how microRNA-93 (miR-93) and tissue inhibitor of matrix metalloproteinase 2 (TIMP2) be involved in OS development. At first, the levels of miR-93 and its predictive target gene TIMP2 were detected in OS and osteoblast cell lines, and 62 pairs OS and adjacent non-OS specimens by real-time PCR and western blot. Then, viability, invasion, and epithelial mesenchymal transition (EMT) of OS cell lines were examined when overexpressed or knocked down miR-93, or overexpressed TIMP2. Finally, the interaction between miR-93 and TIMP2 was evaluated using mutation, gain, and loss experiment. Our data indicated that miR-93 was increased while TIMP2 was decreased in both OS cell lines and tissues. MiR-93 high-expression and TIMP2 low-expression were related with poor overall survival and prognosis of OS patients. Overexpression or knockdown experiment indicated that miR-93 enhanced OS cell viability, invasion, and EMT expression. TIMP2 could inhibit OS cell viability, invasion, and EMT expression. Further, miR-93 directly targeted TIMP2 and negatively regulated TIMP2 level in OS cells. And up-regulation of TIMP2 reversed the effects of miR-93 in OS. Finally, miR-93 regulated the oncogenic functions in OS cells by regulating the expression of TIMP2. In conclusion, our study demonstrates that miR-93 may exert an oncogenic function while TIMP2 may act as a tumor suppressor on OS.