An increasing number of studies have supported the critical regulatory actions of long noncoding RNAs (lncRNAs) in osteosarcoma (OS). However, the detailed roles of adipogenesis regulatory factor-antisense RNA 1 (ADIRF-AS1) in OS have not been comprehensively described. Hence, we first detected ADIRF-AS1 expression in OS and evaluated its clinical significance. Functional experiments were then performed to determine the modulatory role of ADIRF-AS1 in OS progression. ADIRF-AS1 was found to be overexpressed in OS, and the overall survival of patients with OS who had high ADIRF-AS1 levels was shorter than that of those with low levels. ADIRF-AS1 knockdown led to restricted proliferation, migration, and invasivene... More
An increasing number of studies have supported the critical regulatory actions of long noncoding RNAs (lncRNAs) in osteosarcoma (OS). However, the detailed roles of adipogenesis regulatory factor-antisense RNA 1 (ADIRF-AS1) in OS have not been comprehensively described. Hence, we first detected ADIRF-AS1 expression in OS and evaluated its clinical significance. Functional experiments were then performed to determine the modulatory role of ADIRF-AS1 in OS progression. ADIRF-AS1 was found to be overexpressed in OS, and the overall survival of patients with OS who had high ADIRF-AS1 levels was shorter than that of those with low levels. ADIRF-AS1 knockdown led to restricted proliferation, migration, and invasiveness of OS cells and increased apoptosis. Additionally, ADIRF-AS1 downregulation impeded tumor growth . Mechanistically, ADIRF-AS1 acted as a competitive endogenous RNA for microRNA-761 (miR-761) that siphoned miR-761 away from its target, namely insulin receptor substrate 1 (IRS1), leading to IRS1 overexpression. Rescue experiments showed that low levels of miR-761 or restoration of IRS1 could neutralize the effects of ADIRF-AS1 ablation in OS cells. In summary, ADIRF-AS1 exacerbates the oncogenicity of the OS cells by targeting the miR-761/IRS1 axis. Our findings may aid in the advancement of lncRNA-directed therapeutics for OS.
