MicroRNA‑615 functions as a tumor suppressor in osteosarcoma through the suppression of HK2
Limin Sun, Peng Wang, Zhiqiang Zhang, Kai Zhang, Xu Zheng, Siyuan Li, Junsheng Mao
Abstract
At present, the regulatory mechanisms of various microRNAs (miRNAs/miRs) have been elucidated in human cancers including osteosarcoma (OS). This study mainly focused on the role of miR-615 in OS, which has not yet been reported. Ninety-two OS tissues and normal samples were used in this study. Human osteoblast hFOB1.19 cells and OS cell line HOS were utilized to detect the expression of miR-615. The expression of miR-615 and gene expression were assessed by RT-qPCR and western blot analysis. Transwell, MTT and luciferase reporter assays were used to investigate the regulatory mechanism of miR-615 in OS. The results revealed that miR-615 expression was reduced in OS tissues and cells, and was associated with poor clinical outcomes and prognosis in OS patients. In addition, overexpression of miR-615 restrained cell viability and metastasis in OS. Furthermore, hexokinase 2 (HK2) was confirmed as a direct target of miR-615. Upregulation of HK2 was detected in OS tissues. The upregulation of HK2 weakened the tumor-suppressive effect of miR-615 in OS. Moreover, miR-615 blocked epithelial-mesenchymal transition (EMT) and inactivated the PI3K/AKT pathway in OS. To conclude, miR-615 acts as a tumor suppressor in OS, thus miR-615 can be used as a target for OS treatment.