Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha 410011, PR China.
Department of Hematology, Institute of Molecular Hematology, The Second Xiangya Hospital, Central South University, Changsha 410011, PR China.
Pathol Res Pract. 2020 Nov;216(11):153212. doi: 10.1016/j.prp.2020.153212. Epub 2020 Sep 13.
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.
The expression levels of NEAT1 and miR-146b-5p in T-ALL cells were performed by qRT-PCR and NOTCH1 protein level- wwWwas 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 proliferation was measured by using MTT assay and colony formation assay.
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.
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.
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，可发生于任何年龄，症状为虚弱、疲劳、淋巴结肿大或体重减轻。核小体旁聚核体转录本 1（NEAT1）参与 T-ALL 的发生过程，但调控机制尚不清楚。
采用 qRT-PCR 检测 T-ALL 细胞中 NEAT1 和 miR-146b-5p 的表达水平，Western blot 检测 NOTCH1 蛋白水平。双荧光素酶报告基因实验检测 NEAT1 与 miR-146b-5p 以及 miR-146b-5p 与 NOTCH1 的相互作用。MTT 法和集落形成实验检测细胞增殖能力。
T-ALL 细胞中 NEAT1 的表达水平明显升高，而 miR-146b-5p 的水平降低。敲低 NEAT1 或过表达 miR-146b-5p 均可降低 NOTCH1 表达，抑制 T-ALL 细胞增殖。miR-146b-5p 可直接结合 NEAT1 和 NOTCH1 的 3'-UTR。最后，抑制 miR-146b-5p 可消除 NEAT1 敲低对 T-ALL 细胞增殖的影响。
NEAT1 通过海绵吸附 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 调节 T-ALL 进展的作用机制提供了新的见解。
