Long noncoding RNA HIF1A-AS2 facilitates cell survival and migration by sponging miR-33b-5p to modulate SIRT6 expression in osteosarcoma.
BIOCHEMISTRY AND CELL BIOLOGY(2020)
摘要
Long noncoding 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 this study, we demonstrated that HIF1A-AS2 was overexpressed in OS tissues and cells. Downregulation of HIF1A-AS2 significantly affects multiple biological functions in OS cells, including cell proliferation, cell cycle progression, cell apoptosis, cell migration, and cell invasiveness. Mechanistic investigations demonstrated that HIF1A-AS2 can interact with miR-33b-5p and negatively regulate its expression, thereby upregulating the protein expression of miR-33b-5p's target SIRT6. Additionally, in vivo experiments using a xenograft tumor mouse model revealed that downregulation of HIF1A-AS2 suppresses tumor growth in OS. Taken together, a newly identified regulatory mechanism for the lncRNA HIF1A-AS2-miR-33b-5p-SIRT6 axis was systematically studied in OS, which could be a promising target for the treatment of OS.
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关键词
osteosarcoma,lncRNA HIF1A-AS2,miR-33b-5p,SIRT6,cell survival
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