Lupeol inhibits osteosarcoma progression by up-regulation of HMGA2 via regulating miR-212-3p
Jinghua Zhong, Chunlei He, Fang-Tian Xu, Xianyun Xu, Lulin Liu, Mingjun Xu, Zheng Guo, Yili Wang, Jiahua Liao, Yonghong Li
Abstract
BACKGROUND: Osteosarcoma (OS) is a common severe illness globally. Lupeol has been reported to participate in the pathophysiologic properties of various cancers, including OS. This study aimed to explore the effects of lupeol on proliferation, invasion, and apoptosis on OS cells and the underlying mechanism. METHODS: The cell viability of OS cells was determined by 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. The expression levels of miR-212-3p and high-mobility group AT-hook 2 (HMGA2) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) in OS cells. The cell apoptosis and invasion were detected by flow cytometry and transwell invasion assays, respectively. The functional target of miR-212-3p was predicted by online software and confirmed by luciferase reporter assay. The protein level of HMGA2 was measured by western blot analysis. RESULTS: Lupeol suppressed cell viability and invasion, and promoted apoptosis by upregulating the expression of miR-212-3p in OS cells. Knockdown of miR-212-3p restored the anti-tumor effect of lupeol. Interestingly, miR-212-3p directly targeted HMGA2 and suppressed its expression. Moreover, HMGA2 reversed the inhibited impact on viability and invasion, and the promoted effect on apoptosis induced by upregulation of miR-212-3p. Also, lupeol administration exerts its anti-tumor effect by overexpression of miR-212-3p to suppress the expression of HMGA2 in OS cells. CONCLUSION: Lupeol inhibited OS progression by modulating the miR-212-3p/HMGA2 axis in vitro.