LncRNA HIF1A-AS2 promotes osteosarcoma progression by acting as a sponge of miR-129-5p
LncRNA HIF1A-AS2 promotes osteosarcoma progression by acting as a sponge of miR-129-5p
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DOI：
10.18632/aging.102448
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发表时间：
2019-12-31
期刊：
影响因子：
5.2
通讯作者：
Sun, Ruifu
中科院分区：
文献类型：
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作者：
Wang, Xuesong;Peng, Lei;Sun, Ruifu
越来越多的研究表明，长链非编码RNA（lncRNA）在肿瘤的发生、发展中起着重要作用。然而，骨肉瘤和HIF 1AAS 2之间的关系仍然未知。通过qRT-PCR检测骨肉瘤细胞系和样品中HIF 1AAS 2和miR-129- 5 p的表达。细胞计数试剂盒-8（CCK-8）和侵袭试验测定细胞增殖和侵袭能力，双荧光素酶报告基因试验测定HIF 1AAS 2和miR-129- 5 p之间的相互作用。我们发现，HIF 1A-AS 2的表达上调，在骨肉瘤样品中的表达相比，在非癌样品。此外，HIF 1A-AS 2高表达患者的总生存期较短。HIF 1A-AS 2的异位表达促进骨肉瘤细胞增殖、细胞周期进展和侵袭。我们发现miR-129- 5 p的过表达降低了野生型（WT）HIF 1A-AS 2的荧光素酶活性，但对突变型HIF 1A-AS 2没有影响。HIF 1A-AS 2的异位表达抑制MG-63细胞中miR-129- 5 p的表达。我们发现miR-129- 5 p在骨肉瘤中表达下调，并与HIF 1A-AS 2表达呈负相关。此外，miR-129- 5 p的异位表达抑制骨肉瘤细胞增殖、细胞周期进展和侵袭。另外，HIF 1A-AS 2过表达可通过调节miR-129- 5 p促进骨肉瘤细胞的增殖、细胞周期进程和侵袭。提示HIF 1A-AS 2可能是骨肉瘤治疗的潜在靶点。
Increasing studies have demonstrated that long noncoding RNAs (lncRNAs) play vital roles in tumor development and progression. However, the relationship between osteosarcoma and HIF1AAS2 remains unknown. The expression of HIF1AAS2 and miR-129-5p was detected in osteosarcoma cell lines and samples via qRT-PCR. Cell Counting Kit-8 (CCK-8) and invasion assays were performed to determine cell proliferation and invasion ability, and a dual luciferase reporter assay was performed to determine the interaction between HIF1AAS2 and miR-129-5p. We showed that the expression of HIF1A-AS2 was upregulated in the osteosarcoma samples compared with the expression in noncancerous samples. Moreover, patients with high HIF1A-AS2 expression had a shorter overall survival. Ectopic expression of HIF1A-AS2 enhanced osteosarcoma cell proliferation, cell cycle progression and invasion. We found that overexpression of miR-129-5p decreased the luciferase activity of wild-type (WT) HIF1A-AS2 but not mutant HIF1A-AS2. Ectopic expression of HIF1A-AS2 suppressed miR-129-5p expression in MG-63 cells. We demonstrated that miR-129-5p was downregulated in osteosarcoma and was negatively associated with HIF1A-AS2 expression. Furthermore, ectopic expression of miR-129-5p suppressed osteosarcoma cell proliferation, cell cycle progression and invasion. In addition, overexpression of HIF1A-AS2 promoted cell proliferation, cell cycle progression and invasion of osteosarcoma cells through the modulation of miR-129-5p. These results indicated that HIF1A-AS2 might be a potential therapeutic target for osteosarcoma.