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.

中文翻译：

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长的非编码RNA HIF1A-AS2通过海绵化miR-33b-5p调节骨肉瘤中SIRT6的表达来促进细胞存活和迁移。

长的非编码RNA（lncRNA）在各种生理和病理学过程中都已成为重要的调节剂。最近发现，lncRNA HIF1A-AS2可能在多种癌症中发挥致癌作用。然而，lncRNA HIF1A-AS2在骨肉瘤（OS）中的功能和调控机制仍不清楚。在这项研究中，我们证明了HIF1A-AS2在OS组织和细胞中过表达。HIF1A-AS2的下调显着影响OS细胞的多种生物学功能，包括细胞增殖，细胞周期进程，细胞凋亡，细胞迁移和细胞侵袭性。机理研究表明，HIF1A-AS2可以与miR-33b-5p相互作用并对其表达负调控，从而上调miR-33b-5p靶标SIRT6的蛋白表达。另外，使用异种移植肿瘤小鼠模型的体内实验表明，HIF1A-AS2的下调抑制了OS中肿瘤的生长。综上所述，在OS中系统研究了新鉴定的lncRNA HIF1A-AS2-miR-33b-5p-SIRT6轴调控机制，这可能是OS的有希望的靶标。