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miR-133a对肺癌细胞侵袭和迁移的影响及机制

Effects and mechanism of miR-133a on invasion and migration of lung cancer cells.

作者信息

Yu Bing, Pang Jinghua, You Jiawen

机构信息

Department of Thoracic Surgery, Ningbo Fenghua District People's Hospital Ningbo 315500, Zhejiang Province, China.

出版信息

Am J Transl Res. 2022 Feb 15;14(2):728-739. eCollection 2022.

Abstract

OBJECTIVES

To study the role of miR-133a expression in the invasion, proliferation, migration, and apoptosis of lung cancer cells and its mechanism.

METHODS

miR-133a expression levels in human normal lung epithelial cells (BEAS-2B), H441 cell lines and NSCLC tissues were detected by qPCR. The influence of miR-133a mimics on the migration, proliferation and invasion of H441 cells was examined by CCK-8 assay, transwell migration assay, and invasion assay, respectively. Expression of MMP-9 and LASP1 in H441 cellstreated by miR-133a mimics was determined by western blot. Pearson's test was conducted to study the association of miR-133a expression with clinical characteristics of NSCLC patients. The targeted regulation of miR-133a on LASP1 gene expression was detected by the luciferase reporter gene assay.

RESULTS

miR-133a expression was decreased in H441 cells in contrast to that in BEAS-2B cells (P<0.05). Compared with para-carcinoma tissues, miR-133a levels were markedly down-regulated in NSCLC tissues. miR-133a overexpression inhibited the invasion, proliferation, and migration ability of H441 cells and promoted cell apoptosis (all P<0.05). MMP-9 expression levels were also reduced in the miR-133a mimic group. Moreover, miR-133a expression levels were correlated with tumor size and TNM stage. miR-133a overexpression decreased the expression of LASP1, which is the targeted gene of miR-133a.

CONCLUSIONS

miR-133a overexpression can reduce the invasion, proliferation, migration, and matrix metalloproteinase expression of NSCLC cells and promote cell apoptosis. This may be correlated to targeted down-regulation of LASP1 expression.

摘要

目的

研究miR-133a表达在肺癌细胞侵袭、增殖、迁移和凋亡中的作用及其机制。

方法

采用qPCR检测人正常肺上皮细胞(BEAS-2B)、H441细胞系及非小细胞肺癌组织中miR-133a的表达水平。分别通过CCK-8法、Transwell迁移实验和侵袭实验检测miR-133a模拟物对H441细胞迁移、增殖和侵袭的影响。采用蛋白质免疫印迹法检测miR-133a模拟物处理后H441细胞中MMP-9和LASP1的表达。采用Pearson检验研究miR-133a表达与非小细胞肺癌患者临床特征的相关性。通过荧光素酶报告基因实验检测miR-133a对LASP1基因表达的靶向调控。

结果

与BEAS-2B细胞相比,H441细胞中miR-133a表达降低(P<0.05)。与癌旁组织相比,非小细胞肺癌组织中miR-133a水平明显下调。miR-133a过表达抑制了H441细胞的侵袭、增殖和迁移能力,并促进细胞凋亡(均P<0.05)。miR-133a模拟物组中MMP-9表达水平也降低。此外,miR-133a表达水平与肿瘤大小和TNM分期相关。miR-133a过表达降低了miR-133a的靶基因LASP1的表达。

结论

miR-133a过表达可降低非小细胞肺癌细胞的侵袭、增殖、迁移和基质金属蛋白酶表达,并促进细胞凋亡。这可能与靶向下调LASP1表达有关。

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