MicroRNA‐1296‐5p suppresses the proliferation, migration, and invasion of human osteosarcoma cells by targeting NOTCH2

Abstract Osteosarcoma (OS) is a highly aggressive bone tumor with a poor prognosis. MicroRNAs are revealed to exerts essential roles in the carcinogenesis and tumor invasion of OS. But, the function of miR‐1296‐5p and its related mechanism in OS progression have not yet been studied. This study discovered the levels of miR‐1296‐5p in OS and corresponding noncancerous tissues, and we demonstrated that miR‐1296‐5p level was markedly downregulated in tumor specimens as compared with nontumor tissues. In addition, we discovered that miR‐1296‐5p was also underexpressed in OS cells compared with the hFOB1.19 osteoblast cells. Interestingly, the reduced expression of miR‐1296‐5p was confirmed to associated with large tumor size, advanced tumor stages, and distance metastasis, respectively. Patients with OS low‐expressing miR‐1296‐5p showed a prominent shorter survival. In addition, gain‐of‐function assays verified that miR‐1296‐5p overexpression remarkably repressed OS cell proliferation, migration, and invasion. Conversely, depletion of miR‐1296‐5p facilitated the growth and mobility of OS cells. Notably, miR‐1296‐5p inversely modulated notch receptor 2 (NOTCH2) in OS cells. The level of NOTCH2 messenger RNA was negatively correlated with miR‐1296‐5p level in OS samples. NOTCH2 knockdown markedly suppressed the abilities of MG‐63 cell proliferation and mobility. More importantly, the restoration of NOTCH2 prominently rescued miR‐1296‐5p‐induced tumor‐suppressive effects on MG‐63 cells. In conclusion, our study identified the reduced expression of miR‐1296‐5p, which contributed to OS progression. miR‐1296‐5p might be a promising prognostic marker and therapeutic target in OS.