lncRNA TUG1通过miR-143-5p/HIF-1alpha轴促进骨肉瘤转移的机制

Abstract

Early aggressive metastasis of osteosarcoma (OS) leads to rapid progression and poor prognosis. Increasing evidence has demonstrated that long non-coding RNAs (lncRNAs) could serve as crucial regulators to modulate tumour metastasis. In this study, we reported the critical role of lncRNA TUG1 in determining OS metastasis. TUG1 was significantly upregulated in OS tissues and associated with tumour size, distant metastasis, TNM stage, and overall and recurrence-free survival, which further indicated poor prognosis. Furthermore, CAFs-derived TGF-β could upregulate TUG1 expression, and the crosstalk between CAFs and OS cells induced TUG1 to promote OS cell metastasis. Dysregulated TUG1 expression could act as an miRNA “sponge” to competitively protect the HIF-1α mRNA 3′UTR from miR-143-5p. Our study emphasised the effects of TUG1 in OS and demonstrated a novel axis by which TUG1 regulated OS cell metastasis, angiogenesis, and proliferation in vivo and in vitro. Collectively, TUG1 might be a prognostic indicator for OS and could be a therapeutic target for OS.