Long noncoding RNA HIF1A-AS2 facilitates cell survival and migration by sponging miR-33b-5p to modulate SIRT6 expression in osteosarcoma
Long noncoding RNA HIF1A-AS2 facilitates cell survival and migration by sponging miR-33b-5p to modulate SIRT6 expression in osteosarcoma
复制标题
长链非编码RNA HIF1A-AS2通过海绵miR-33b-5p调节SIRT6在骨肉瘤中的表达，促进细胞存活和迁移
DOI：
10.1139/bcb-2019-0171
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发表时间：
2020-04-01
影响因子：
2.9
通讯作者：
He, Jian
中科院分区：
文献类型：
--
作者：
Lin, Hang;Zhao, Zhenxu;He, Jian
长链非编码RNA（longnoncodingRNA，lncRNA）是近年来发现的一类重要的生物学调节因子，参与多种生理和病理过程。最近发现lncRNA HIF 1A-AS 2在多种癌症中发挥致癌作用。然而，lncRNA HIF 1A-AS 2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HIF 1A-AS 2在OS组织和细胞中过表达。HIF 1A-AS 2的下调显著影响OS细胞的多种生物学功能，包括细胞增殖、细胞周期进展、细胞凋亡、细胞迁移和细胞侵袭。机制研究表明，HIF 1A-AS 2可以与miR-33 b-5 p相互作用并负调控其表达，从而上调miR-33 b-5 p靶向SIRT 6的蛋白表达。此外，使用异种移植肿瘤小鼠模型的体内实验显示，HIF 1A-AS 2的下调抑制OS中的肿瘤生长。总之，系统地研究了OS中新鉴定的lncRNA HIF 1A-AS 2-miR-33 b-5 p-SIRT 6轴的调节机制，这可能是治疗OS的有希望的靶点。
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.