Long noncoding RNA HIF1A-AS2 facilitates cell survival and migration by sponging miR-33b-5p to modulate SIRT6 expression in osteosarcoma.

Abstract

Long non-coding RNAs (lncRNAs) are emerging as vital regulators in various physiological and pathological processes. It was recently found that lncRNA HIF1A-AS2 could play oncogenic roles in several cancers. However, the function and regulatory mechanism of lncRNA HIF1A-AS2 in osteosarcoma (OS) remain largely unclear. In the present study, we demonstrated that HIF1A-AS2 was overexpressed in OS tissues and cells. HIF1A-AS2 downregulation could remarkably affect multiple OS cell biological functions, including cell proliferation, cell cycle progression, cell apoptosis, cell migration and cell invasion. Mechanistic investigations demonstrated that HIF1A-AS2 can interact with miR-33b-5p and negatively regulate its expression, thereby upregulate the protein expression of miR-33b-5p's target SIRT6. Additionally, in vivo experiments using a xenograft tumor mouse model revealed that HIF1A-AS2 downregulation suppressed tumor growth in OS. Taken together, a newly identified regulatory mechanism of lncRNA HIF1A-AS2/miR-33b-5p/SIRT6 axis was systematically studied in OS, which may hold promise as a promising target for treatment.