Chen L-M, Niu Y-D, Xiao M, Li X-J, Lin H
Department of Oncology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Eur Rev Med Pharmacol Sci. 2020 May;24(9):4810-4821. doi: 10.26355/eurrev_202005_21170.
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.
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.
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.
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.
近年来，长链非编码RNA（lncRNA）已被确定在癌症的形成和发展中发挥重要作用。然而，lncRNA在非小细胞肺癌（NSCLC）中的调控机制尚未完全阐明。
通过定量实时聚合酶链反应（qRT-PCR）检测每组中NEAT1、miR-376b-3p和SULF1的表达。通过蛋白质免疫印迹法检测SULF1、磷酸化丝裂原活化蛋白激酶（p-MAPK）、丝裂原活化蛋白激酶（MAPK）、磷酸化蛋白激酶B（p-Akt）、蛋白激酶B（Akt）和甘油醛-3-磷酸脱氢酶（GAPDH）的蛋白表达。采用MTT法检测每组细胞的增殖情况。采用Transwell法评估每组细胞的侵袭和迁移能力。通过流式细胞术评估细胞凋亡情况。使用荧光素酶报告基因检测法确定NEAT1、miR-376b-3p和SULF1之间的关系。
在本研究中，NSCLC组织和细胞中NEAT1和SULF1的表达上调。值得注意的是，敲低NEAT1和SULF1可抑制NSCLC细胞的增殖、迁移和侵袭，并促进细胞凋亡。此外，在NSCLC细胞中，NEAT1通过与miR-376b-3p结合来调节SULF1的表达。否则，通过提高NSCLC细胞中SULF1的表达，可逆转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来抑制MAPK和Akt信号通路。
在本研究中，我们发现lncRNA NEAT1在NSCLC中通过靶向has-miR-376b-3p/SULF1轴来调节细胞增殖、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，以影响NSCLC的细胞进程，为肺癌发病机制提供了一条新的调控途径。
