miR-216a调控ARID1A在非小细胞肺癌作用及肿瘤CT表现

miR-216a downregulated the tumor suppressor gene ARID1A in non-small cell lung cancer and CT findings

目的观察miR-216a和ARID1A对非小细胞肺癌(NSCLC)细胞增殖、周期和迁移能力的影响,揭示miR-216a在NSCLC中的作用及机制。方法前瞻性研究。收集2017年3月至2020年3月上海市浦东新区人民医院NSCLC手术且血浆miR-26a异常表达患者126例,所有患者进行肺部病灶的CT测量,检测ARID1A在NSCLC组织和癌旁正常组织中的表达水平;TargetScan和双荧光素酶报告基因试验筛选并证实miR-216a的靶基因,qRT-PCR和Western blot检测在A549细胞中转染miR-216a模拟物对ARID1A表达的影响。CCK8法、流式细胞法和Transwell实验分别检测miR-216a和ARID1A对A549细胞增殖、S期细胞比值及迁移的影响。建立肺癌裸鼠移植瘤模型,检测miR-216a对瘤体生长的影响。结果高表达miR-216a患者肺部病灶的轴位最大长径、与其垂直的最大短径、冠状位最大垂直长径均较miR-216a低表达者大,分别(3.83±0.59)cm、(2.38±0.41)cm、(4.13±0.72)cm比(2.31±0.45)cm、(1.69±0.34)cm、(2.41±0.48)cm;并且NSCLC组织中ARID1A的表达水平明显降低,miR-216a能靶向调控ARID1A的表达;在A549细胞中过表达miR-216a能促进细胞的增殖,S期阻滞和迁移能力,但上调ARID1A能逆转miR-216a的调控效果。在肺癌裸鼠移植瘤模型中,上调miR-216a的表达能抑制ARID1A并促进瘤体生长。结论miR-216a能通过靶向调控ARID1A的表达促进A549细胞的生物学行为及裸鼠中瘤体的生长,提示miR-216a对NSCLC可能具有促癌的作用。

Objective To analyze the regulatory effect of miR-216a on ARID1A,to observe the effects of miR-216a and ARID1A on the proliferation,cell cycle and migration of NSCLC cells,and to reveal the role and mechanism of miR-216a in NSCLC.Methods Perspective reseach was involoved.CT measurements of abnormal plasma miR-26a expression in patients with non-small cell lung cancer,and ARID1A in NSCLC tissues and adjacent normal tissues were detected.The target gene of miR-216a was screened and confirmed by targetscan and double luciferase reporter gene assay,qRT-PCR and Western blot were used to detect the effect of miR-216a mimics transfection on ARID1A expression in A549 cells.The effects of miR-216a and ARID1A on the proliferation,S phase cell ratio and migration of A549 cells were detected by CCK8,flow cytometry and Transwell assay,respectively.A nude mice xenograft model of NSCLC was established to detect the effect of miR-216a on tumor growth.Results Themaximum axial diameter,the maximum vertical short diameter and the maximum vertical long diameter of plasma in patients with high expression of miR-216a were larger.The expression level of ARID1A in NSCLC tissues was significantly lower than that of adjacent normal tissues.miR-216a could target and regulate the expression of ARID1A.Overexpression of miR-216a in A549 cells promoted cell proliferation,S stage arrest and migration,but up-regulation of ARID1A could reverse the regulatory effect of miR-216a.In the xenograft model of nude mice with lung cancer,upregulation of miR-216a inhibited ARID1A and promoted tumor growth.Conclusions miR-216a may promote the biological behavior of A549 cells and tumor growth in nude mice by targeting the expression of ARID1A,suggesting that miR-216a may have a pro-cancer effect on NSCLC.