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。

H. Lin, Zhenxu Zhao, Yi Hao, Jun He, Jian He
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引用次数: 19

摘要

长链非编码rna (lncRNAs)在各种生理和病理过程中发挥着重要的调节作用。最近发现lncRNA HIF1A-AS2可能在几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在很大程度上仍不清楚。在本研究中,我们证实了HIF1A-AS2在OS组织和细胞中过表达。HIF1A-AS2下调可显著影响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,HIF1A-AS2可与miR-33b-5p相互作用,负向调控其表达,从而上调miR-33b-5p靶点SIRT6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,HIF1A-AS2下调可抑制OS中的肿瘤生长。综上所述,我们在OS中系统地研究了一种新发现的lncRNA HIF1A-AS2/miR-33b-5p/SIRT6轴的调控机制,这可能是一种有希望的治疗靶点。
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Long noncoding RNA HIF1A-AS2 facilitates cell survival and migration by sponging miR-33b-5p to modulate SIRT6 expression in osteosarcoma.
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.
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