Lupeol inhibits osteosarcoma progression by up-regulation of HMGA2 via regulating miR-212-3p
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(2020) 15:374
RESEARCH ARTICLE
Open Access
Lupeol inhibits osteosarcoma progression by up-regulation of HMGA2 via regulating miR-212-3p Jinghua Zhong1†, Chunlei He2†, Fangtian Xu2, Xianyun Xu3, Lulin Liu2, Mingjun Xu1, Zheng Guo1, Yili Wang1, Jiahua Liao1 and Yonghong Li4*
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. Keywords: OS, Lupeol, miR-212-3p, HMGA2, Viability, Invasion, Apoptosis
Introduction Osteosarcoma (OS) is the most frequent mesenchymal sarcoma derived from the bone matrix synthesized and secreted by neoplastic cells [1]. Although the survival rate of patients with OS significantly improved by modern treatment [2, 3], 25–35% of patients with initial non* Correspondence: [email protected] † Jinghua Zhong and Chunlei He contributed equally to this work. 4 Department of Oncology, The First Hospital of Tianmen City of Hubei Province, No. 1, East Renmin Avenue, Tianmen 431700, Hubei, China Full list of author information is available at the end of the article
metastatic disease subsequently metastasized, which remains the leading cause of death [4]. Over the two decades, there are many accumulating evidence manifest that unbalances of molecule-regulated participated in the pathological progress of OS. Whereas, the latent mechanism of OS still needs to explore. Thus, it is essential to find novel biomarkers for optimizing therapeutic strategies and predictions for clinical outcomes. Lupeol (Lup-20(29)-en-3β-ol), a significant lupanetype triterpene existed in natural plants of garden stuff [5, 6],
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