LINC00612 functions as a ceRNA for miR-214-5p to promote the proliferation and invasion of osteosarcoma in vitro and in vivo.

Long noncoding RNAs (lncRNAs) are key regulators that participate in multiple biological processes, including cancer formation and progression. The biological function and molecular mechanism of LINC00612 in the progression of osteosarcoma has not been elucidated before. In this study, we evaluated the expression of LINC00612 in osteosarcoma by qRT-PCR. ShRNA-induced LINC00612 downregulation and plasmid-transduced LINC00612 overexpression were conducted in U2OS and HOS cells. The in vitro functional effects of LINC00612 downregulation and overexpression on osteosarcoma cells were evaluated by CCK-8 assay, colony formation assay, scratch assay, transwell invasion assay and flow cytometry; in vivo tumor xenografts were conducted in nude mice. The effects of LINC00612 downregulation and overexpression on epithelial-mesenchymal transition (EMT) were assessed by scratch assay, transwell assay and qRT-PCR. The possibility of LINC00612 acting as a competing endogenous RNA (ceRNA) to target microRNA miR-214-5p was examined by dual-luciferase reporter assay. Then, miR-214-5p was downregulated or overexpressed to examine its effect on invasion and SOX4 expression in osteosarcoma cells. LINC00612 was found to be significantly upregulated in osteosarcoma cells and metastatic osteosarcoma. LINC00612 overexpression promoted the proliferation, invasion and in vivo explant growth of osteosarcoma. In addition, LINC00612 overexpression regulated EMT by elevating the expression of ZEB1, Snail, and Fibronectin 1 and inhibiting E-cadherin. MiR-214-5p was confirmed to be a ceRNA of LINC00612. LINC00612 overexpression upregulated SOX4 by inhibiting miR-214-5p. Our study shows that LINC00612 plays an important role in regulating the proliferation and invasion of osteosarcoma by endogenously competing with miR-214-5p and mediating EMT.