MALAT1调控miR-19b-3p/HIF-1α分子轴参与非小细胞肺癌的发生发展

MALAT1 Involves in the Pathogenesis of Non-small Cell Lung Cancer by Regulating the miR-19b-3p/HIF-1αMolecular Axis

目的探讨MALAT1调控miR-19b-3p/HIF-1α影响非小细胞肺癌(NSCLC)的发病机制。方法采用实时荧光定量PCR(qRT-PCR)检测MALAT1、miR-19b-3p在NSCLC肺癌组织和NSCLC细胞系中的表达水平。过表达miR-19b-3p和敲除MALAT1后,采用qRT-PCR和Western blot检测A549细胞中MALAT1、miR-19b-3p、缺氧诱导因子-1α(HIF-1α)和血管内皮生长因子(VEGF)表达水平的变化。采用细胞增殖毒性检测试剂盒(CCK-8)和流式细胞术检测细胞增殖、细胞周期和凋亡情况。采用Transwell实验检测细胞迁移及侵袭能力。结果在NSCLC癌组织及NSCLC细胞系中MALAT1表达升高、miR-19b-3p表达降低,并且MALAT1与miR-19b-3p表达水平呈负相关(r=-0.8969,P<0.01);过表达miR-19b-3p及敲除MALAT1可使A549细胞中miR-19b-3p基因表达升高,MALAT1、HIF-1α及VEGF基因表达下降。过表达miR-19b-3p使A549细胞增殖能力、分裂能力、侵袭迁移能力下降,凋亡率增加。结论MALAT1可能靶向miR-19b-3p调节HIF-1α/VEGF参与非小细胞肺癌发生发展。

Objective To investigate the effect of MALAT1 on the pathogenesis of non-small cell lung cancer(NSCLC)by regulating miR-19b-3p/HIF-1α.Methods The expression levels of MALAT1 and miR-19b-3p in NSCLC tissues and NSCLC cell lines were detected by real-time quantitative PCR(qRT-PCR).Overexpression and knockout of genes were performed to detect the expression levels of MALAT1,miR-19b-3p,hypoxia-inducible factor-1α(HIF-1α),and vascular endothelial growth factor(VEGF)in A549 cells.Cell proliferation,cell cycle,and apoptosis were detected by cell proliferative toxicity test kit(CCK-8)and flow cytometry.Transwell experiment was used to detect cell migration and invasion.Results MALAT1 expression was elevated in NSCLC tissues and NSCLC cell lines,while miR-19b-3p expression was decreased,and the expression levels of MALAT1 and miR-19b-3p were negatively correlated.Overexpression of miR-19b-3p and knockout of MALAT1 increased the expression of miR-19b-3p genes and decreased expression of MALAT1,HIF-1αand VEGF genes in A549 cells.Overexpression of miR-19b-3p reduced A549 cell proliferation,division,invasion and migration,and increased apoptosis rate.Conclusion MALAT1 may modulate HIF-1α/VEGF by targeting miR-19b-3p,thus participating in the occurrence and development of non-small cell lung cancer.