LncRNA-NEAT1 promotes proliferation of T-ALL cells via miR-146b-5p/NOTCH1 signaling pathway
LncRNA-NEAT1 promotes proliferation of T-ALL cells via miR-146b-5p/NOTCH1 signaling pathway
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LncRNA-NEAT1通过miR-146b-5p/NOTCH1信号通路促进T-ALL细胞增殖
DOI：
10.1016/j.prp.2020.153212
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发表时间：
2020-11-01
影响因子：
2.8
通讯作者：
Xu, Yun-Xiao
中科院分区：
文献类型：
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作者：
Luo, Yun-Ya;Wang, Zhi-Hua;Xu, Yun-Xiao
背景：T细胞急性淋巴细胞白血病(T-ALL)是一种造血系统的恶性肿瘤，可在任何年龄发展，表现为虚弱、乏力、淋巴结肿大或体重减轻等症状。核副斑点组装转录本1(NEAT1)参与了T-ALL的发病过程，但其调控机制尚不清楚。方法：采用定量RT-PCR方法检测NEAT1和miR-146b-5p在T-ALL细胞中的表达水平，用Western印迹法检测NOTCH1蛋白水平。用双荧光素酶报告基因检测NEAT1与miR-146b-5p、miR-146b-5p与NOTCH1的相互作用。结果：T-ALL细胞中NEAT1的表达水平显著升高，miR-146b-5p的表达水平显著降低。NEAT1基因敲除或miR-146b-5p过表达可降低NOTCH1的表达，抑制T-ALL细胞的增殖。MiR-146b-5p直接与NEAT1和NOTCH1 3‘-UTR结合。结论：NEAT1通过海绵miR-146b-5p上调NOTCH1的表达促进T-ALL细胞的增殖。本研究结果为NEAT1调控T-ALL进程的作用机制提供了新的视角。
Background: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant tumor of the hematopoietic system, which can develop at any age, with the symptoms of weakness, fatigue, enlarged lymph nodes, or weight loss. Nuclear paraspeckle assembly transcript 1 (NEAT1) is involved in the process of T-ALL, but the regulatory mechanism is still not known clearly.Methods: The expression levels of NEAT1 and miR-146b-5p in T-ALL cells were performed by qRT-PCR and NOTCH1 protein levelwwWwas determined by western blot assay. Dual-luciferase reporter assay was used to detect the interaction between NEAT1 and miR-146b-5p, as well as miR-146b-5p and NOTCH1. The cell pro-liferation was measured by using MTT assay and colony formation assay.Results: The expression levels of NEAT1 were markedly increased, but miR-146b-5p levels were reduced in T-ALL cells. Knockdown of NEAT1 or overexpression of miR-146b-5p decreased NOTCH1 expression, inhibited the proliferation of T-ALL cells. MiR-146b-5p bound both NEAT1 and NOTCH1 3 '-UTR directly. Finally, inhibition of miR-146b-5p could abrogate the effects of NEAT1 knockdown on the proliferation of T-ALL cells.Conclusion: NEAT1 promotes the proliferation of T-ALL cells by sponging miR-146b-5p to upregulate the expression of NOTCH1. The results of this study provide new insight into the action mechanism of NEAT1 modulating T-ALL progression.