LncRNA NEAT1 regulated cell proliferation, invasion, migration and apoptosis by targeting has-miR-376b-3p/SULF1 axis in non-small cell lung cancer
LncRNA NEAT1 regulated cell proliferation, invasion, migration and apoptosis by targeting has-miR-376b-3p/SULF1 axis in non-small cell lung cancer
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DOI：
10.26355/eurrev_202005_21170
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发表时间：
2020-05-01
影响因子：
3.3
通讯作者：
Lin, H.
中科院分区：
文献类型：
--
作者：
Chen, L-M;Niu, Y-D;Lin, H.
目的：最近，lncRNA已被确定在癌症形成和发展中发挥重要作用。然而，lncRNA在NSCLC中的调控机制尚未得到充分探索。患者和方法：通过定量实时聚合酶链反应（qRT-PCR）检测各组中NEAT1、miR-376b-3p和SULF1的表达。通过Western blot检测SULF1、p-MAPK、MAPK、p-Akt、Akt和GAPDH的蛋白表达。 MTT法检测各组细胞增殖情况。采用Transwell实验评估各组细胞的侵袭和迁移能力。用流式细胞术评估细胞凋亡。使用荧光素酶报告基因检测确定NEAT1、miR-376b-3p和SULF1之间的关系。结果：在本研究中，NEAT1和SULF1的表达在NSCLC组织和细胞中上调。值得注意的是，敲低 NEAT1 和 SULF1 可以抑制 NSCLC 细胞的增殖、迁移和侵袭，并促进细胞凋亡。此外，NEAT1 通过与 NSCLC 细胞中的 miR-376b-3p 结合来调节 SULF1 表达。另外，通过提高 NSCLC 细胞中 SULF1 的表达，可以逆转 NEAT1 对细胞生长和凋亡的影响。同时，si-NEAT1转染通过调节NSCLC细胞中的SULF1抑制MAPK和Akt信号通路。结论：在本研究中，我们发现lncRNA NEAT1通过靶向miR-376b-3p/SULF1轴来调节NSCLC细胞的增殖、侵袭、迁移和凋亡。此外，NEAT1的调控网络参与MAPK和Akt的磷酸化水平影响NSCLC的细胞进展，为肺癌的发病机制提供了新的调控途径。
OBJECTIVE: Recently, lncRNA has been determined to play an important role in cancer formation and development. However, the regulatory mechanism of lncRNA in NSCLC has not been fully explored.PATIENTS AND METHODS: The expression of NEAT1, miR-376b-3p, and SULF1 was detected in each group via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The proteins expression of SULF1, p-MAPK, MAPK, p-Akt, Akt, and GAPDH were measured via Western blot. MTT assay was applied to detect cell proliferation in each group. Transwell assay was used to assess cell invasion and migration of each group. Cell apoptosis was assessed with flow cytometry. The relationship among NEAT1, miR-376b-3p, and SULF1 was determined using Luciferase reporter assay.RESULTS: In this study, the expression of NEAT1 and SULF1 was upregulated in NSCLC tissues and cells. Of note, the knockdown of NEAT1 and SULF1 could inhibit cell proliferation, migration, and invasion and promote cell apoptosis in NSCLC. Moreover, NEAT1 regulated SULF1 expression via binding to miR-376b-3p in NSCLC cells. Otherwise, the effects of NEAT1 on cell growth and apoptosis were reversed by improving the SULF1 expression in NSCLC cells. Meanwhile, si-NEAT1 transfection inhibited MAPK and Akt signaling pathway by modulating SULF1 in NSCLC cells.CONCLUSIONS: In this study, we found that lncRNA NEAT1 regulated cell proliferation, invasion, migration, and apoptosis by targeting has miR-376b-3p/SULF1 axis in NSCLC. Moreover, the regulatory network of NEAT1 participated in the phosphorylation levels of MAPK and Akt to affect cell progression of NSCLC, providing a new regulatory pathway in the pathogenesis of lung cancer.