Cancer Management and Research (Sep 2020)
MicroRNA-431-5p Inhibits the Tumorigenesis of Osteosarcoma Through Targeting PANX3
Abstract
Shengliang Sun,1,* Lei Fu,1,* Gen Wang,1 Jianli Wang,1 Liping Xu2 1Department of Orthopedic Trauma, The 89th Army Hospital of the Chinese People’s Liberation Army, Weifang, Shandong, People’s Republic of China; 2Department of Oncology, The 89th Army Hospital of the Chinese People’s Liberation Army, Weifang, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liping Xu Tel +86 536-5019053Email [email protected]: This study aimed to evaluate the regulatory role of miR-431-5p on the tumorigenesis of osteosarcoma (OS) and the underlying mechanism involving pannexin 3 (PANX3).Methods: qRT-PCR was applied to measure the expression of miR-431-5p in OS tissues and cells. PANX3 and miR-431-5p were overexpressed in U2OS and HOS cells. The cell viability and apoptosis were determined by MTT and FITC/PI double staining assay, respectively. Transwell assay was performed to detect cell migration and invasion. The protein expression of cleave-caspase-3 and MMP-2/-9 was detected by Western blot. The target relationship between miR-431-5p and PANX3 was predicated by ENCORI and identified by DLR assay. The anti-tumor effect of miR-431-5p was further analyzed in a xenograft tumor model in mice.Results: MiR-431-5p expression was down-regulated in OS tissues and negatively correlated with lymph node metastasis and TNM stage. Over-expression of miR-431-5p induced cell apoptosis, inhibited cell proliferation, migration and invasion, up-regulated cleave-caspase-3, and down-regulated MMP-2 and -9 in OS cells. Over-expression of miR-431-5p also inhibited the growth of tumor xenografts in mice. In addition, PANX3 was a target of miR-431-5p. Over-expression of PANX3 reversed the anti-tumor effect of miR-431-5p mimics on U2OS and HOS cells.Conclusion: Up-regulation of miR-431-5p suppressed the tumorigenesis of OS via targeting PANX3.Keywords: osteosarcoma, microRNA-431-5p, pannexin 3, proliferation, migration
