代谢相关肺腺癌转录子1调节HMGB1促进骨肉瘤发展的机制研究

Recently, emerging evidence has demonstrated that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), one of the long non-coding RNAs (lncRNAs), contributes to the initiation and development of many solid tumors, including osteosarcoma (OS). Multiple studies from human OS cell lines and tumor samples have suggested an oncogenic role of MALAT1 in OS tumorigenesis and metastasis, but the effects and mechanisms are not unanimous. Here, we showed that MALAT1 was significantly increased in human OS cell lines and tissues and promoted OS cell growth, while knocking down of MALAT1 significantly suppressedOS cell growth. Interestingly, we detected significant downregulation of miR-142, a suppressor of OS growth, in OS tissues, and the expression of miR-142 was negatively correlated with MALAT1. We have also performed luciferase reporter assay and a direct interaction was shown between miR-142 and MALAT1 via a putative miR-142 binding site within the MALAT1 3'-untranslated region (3'-UTR). Meanwhile, we detected significant upregulation of HMGB1 in OS tissues compared with the adjacent normal tissues. HMGB1 promoted OS cell growth and has been shown as a direct target of miR-142. HMGB1 positively correlated with MALAT1 but negatively correlated with miR-142. The miR-142 dependentMetastasis-associated lung adenocarcinoma transcript1 promotes osteosarcoma development by regulation of HMGB1 via miR-142 HMGB1 activation was required for MALAT1 induced OS cell growth. Moreover, a direct interaction between miR-142 and HMGB1 3'-UTR was demonstrated by mutation and luciferase reporter assay. Together, our results support a MALAT1/miR-142/HMGB1 axis in OS cell proliferation and tumor progression. MALAT1 promoted OS cell growth through inhibition of miR-142 and by targeting HMGB1.