LEF1-AS1 accelerates tumorigenesis in glioma by sponging miR-489-3p to enhance HIGD1A
LEF1-AS1 accelerates tumorigenesis in glioma by sponging miR-489-3p to enhance HIGD1A
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DOI：
10.1038/s41419-020-02823-0
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发表时间：
2020-08-11
影响因子：
9
通讯作者：
Guo, Zhilin
中科院分区：
文献类型：
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作者：
Cheng, Zhihua;Wang, Guangyu;Guo, Zhilin
长链非编码淋巴增强子结合因子1反义RNA 1（LEF 1-AS 1）已被证实与多种肿瘤有关，但其在胶质瘤中的作用尚未完全阐明。因此，在这项研究中，我们测试了LEF 1-AS 1表达在胶质瘤组织和细胞系中显著上调。此外，LEF 1-AS 1基因的敲低在体外抑制胶质瘤细胞的增殖而激活凋亡，并且在体内也抑制肿瘤的生长。RNA pull-down和荧光素酶报告基因检测证实LEF 1-AS 1可与miR-489- 3 p结合。此外，miR-489- 3 p在胶质瘤细胞中表达下调。此外，miR-489- 3 p缺失部分抵消了LEF 1-AS 1敲减介导的增殖和凋亡功能。此外，被鉴定为miR-489- 3 p的靶基因的HIGD 1A在胶质瘤细胞中上调。HIGD 1A基因沉默可限制胶质瘤的发生发展。在拯救试验中，上调HIGD 1A弥补了LEF 1-AS 1沉默对胶质瘤细胞生长的抑制作用。综上所述，我们的研究进一步证实了LEF 1-AS 1/miR-489- 3 p/HIGD 1A轴在胶质瘤中的调控机制，提示以LEF 1-AS 1为靶点的治疗可能是未来胶质瘤治疗的一种有前景的方法。
Long non-coding (lncRNA) lymphoid enhancer-binding factor 1 antisense RNA 1 (LEF1-AS1) has been validated to be implicated in manifold cancers, whereas its function in glioma has not been understood thoroughly. Hence, in this study, we tested that LEF1-AS1 expression was significantly upregulated in glioma tissues and cell lines. Besides, knockdown of LEF1-AS1 repressed cell proliferation while activated apoptosis in glioma cells in vitro, and also suppressed tumor growth in vivo. RNA pull-down and luciferase reporter assays affirmed that LEF1-AS1 could bind with miR-489-3p. In addition, miR-489-3p expression was downregulated in glioma cells. Moreover, miR-489-3p depletion partly offset LEF1-AS1 knockdown-mediated function on proliferation and apoptosis. Further, HIGD1A identified as the target gene of miR-489-3p was upregulated in glioma cells. HIGD1A silence could restrict the process of glioma. In rescue assays, upregulation of HIGD1A remedied the inhibitory impacts of LEF1-AS1 silence on glioma cell growth. In summary, our studies corroborated the regulatory mechanism of LEF1-AS1/miR-489-3p/HIGD1A axis in glioma, suggesting that targeting LEF1-AS1 might be a promising method for glioma therapy in the future.