LncRNA TUG1 promotes cell proliferation and suppresses apoptosis in osteosarcoma by regulating miR-212-3p/FOXA1 axis

Abstract

BackgroundLncRNA taurine upregulated gene 1 (TUG1) was reported to act as a possible oncogene in osteosarcoma (OS) development. However, the underlying molecular basis of TUG1 involved in the progression of OS remains to be thoroughly investigated. MethodsThe expressions of TUG1 and miR-212-3p in OS tissues and cells were examined by RT-qPCR. Cell proliferation, apoptosis, caspase-3 activity, protein levels of BCL2, Bax, and forkhead box A1 (FOXA1) were detected by colony formation assay, MTT assay, flow cytometry analysis, caspase-3 activity assay, and western blot. Luciferase reporter assay, RNA immunoprecipitation (RIP) assay, and RT-qPCR were used to explore the interaction between TUG1, FOXA1 and miR-212-3p. Tumor xenograft mouse model was used to confirm the biological role of TUG in OS in vivo. ResultsElevated TUG1 and FOXA1 expression and reduced miR-212-3p expression were observed in OS tissues and cells. TUG1 knockdown suppressed OS cell proliferation and promoted apoptosis. TUG1 functioned as a ceRNA of miR-212-3p and suppressed miR-212-3p expression. miR-212-3p inhibition reversed the effect of TUG1 knockdown on OS cell proliferation and apoptosis. In addition, FOXA1 was identified as a target of miR-212-3p and TUG1 functioned as a ceRNA to upregulate FOXA1 by sponging miR-212-3p in OS cells. FOXA1 up-regulation abolished the effects of miR-212-3p on OS cell proliferation and apoptosis. ConclusionTUG1 promoted OS cell proliferation and suppressed apoptosis by regulating the miR-212-3p/FOXA1 axis. Therefore, TUG1/miR-212-3p/FOXA1 axis may be a promising therapeutic target in OS treatment.