首页|LncRNA MALAT1通过靶向miR-146a调节PI3K/Akt信号通路影响胃癌细胞的增殖、迁移和侵袭

LncRNA MALAT1通过靶向miR-146a调节PI3K/Akt信号通路影响胃癌细胞的增殖、迁移和侵袭

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目的 探究长链非编码RNA(long non-coding RNA，LncRNA)肺腺癌转移相关转录子1(me-tastasis-associated lung adenocarcinoma transcript 1，MALAT1)通过调节 miR-146a 对胃癌(gastric cancer，GC)细胞的增殖、迁移和侵袭的影响及其机制。方法 收集GC组织和配对正常胃上皮组织，将GC细胞MNK-45 分为空白对照(blank control，BC)组(未转染)、MALAT1 siRNA-NC组(转染MALAT1 siRNA-NC)、MALAT1 siRNA组(转染MALAT1 siRNA)、miR-146a mimics-NC组(转染miR-146a mimics-NC)、miR-146a mimics 组(转染 miR-146a mimics)、MALAT1 siRNA+miR-146a inhibitor-NC组(共转染 MALAT1 siRNA+miR-146a inhibitor-NC)、MALAT1 siRNA+miR-146a inhibitor组(共转染MALAT1 siRNA+miR-146a inhibitor)。定量荧光PCR(qRT-PCR)检测胃组织或细胞中MALAT1、miR-146a表达量;CCK-8 法和克隆形成实验检测细胞增殖能力;Transwell法检测细胞侵袭和迁移能力;RNA pull down实验、双荧光素酶报告实验分析 MALAT1 和 miR-146a的结合情况;Western blot检测磷脂酰肌醇3 激酶(phosphatidylinositol 3-kinase，PI3K)/蛋白激酶B(protein kinase B，Akt)通路蛋白及 c-Myc、基质金属蛋白酶 9(matrix metalloproteinase 9，MMP9)蛋白表达量。结果 转染MALAT1 siRNA可明显降低MNK-45 细胞的MALAT1 表达量，敲低MALAT1 或过表达miR-146a可降低细胞活力、克隆能力、迁移和侵袭，增加miR-146a表达，降低PI3Kp85α、PI3Kp85β、c-Myc、MMP9 蛋白表达量及p-Akt/Akt水平;MALAT1 可结合并靶向下调miR-146a表达;低表达miR-146a可逆转敲低MALAT1 对MNK-45 细胞增殖、迁移和侵袭的抑制效应。结论 MALAT1 可能作为 ceRNA 吸附并降解 miR-146a，敲低 MALAT1 可上调 miR-146a表达，并通过PI3K/Akt通路抑制GC细胞增殖、迁移和侵袭。
LncRNA MALAT1 regulates the PI3 K/Akt signaling pathway by targeting miR-146a to affect the proliferation,migration and invasion of gastric cancer cells
Objective To explore the effects and mechanism of long non-coding RNA(LncRNA)metastasis-associated lung adenocarcinoma transcript 1(MALAT1)on the proliferation,migration and invasion of gastric cancer(GC)cells by regulating miR-146a.Methods Transfection of MALAT1 siRNA was able to obviously reduce the expression of MALAT1 in MNK-45 cells.Knockdown of MALAT1 or overexpression of miR-146a was able to reduce cell viability,cloning ability,migration and invasion,increase miR-146a expression,and reduce the p-Akt/Akt level and protein expressions of PI3Kp85α,PI3Kp85β,c-Myc and MMP9;MALAT1 was able to bind to and target down-regulation of miR-146a expression;low expression of miR-146a was able to reverse the inhibitory effects of knocking down MALAT1 on the proliferation,migration and invasion of MNK-45 cells.Results Transfection of MALAT1 siRNA was able to obviously reduce the expression of MALAT1 in MNK-45 cells.Knockdown of MALAT1 or overexpression of miR-146a was able to reduce cell viability,cloning ability,migration and invasion,increase miR-146a expression,and reduce the p-Akt/Akt level and protein expressions of PI3Kp85α,PI3Kp85β,c-Myc and MMP9;MALAT1 was able to bind to and target down-regulation of miR-146a expression;low expression of miR-146a was able to reverse the inhibitory effects of knocking down MALAT1 on the proliferation,migration and invasion of MNK-45 cells.Conclusion MALAT1 may be used as ceRNA to adsorb and degrade miR-146a.Knockdown of MALAT1 can up-regulate the expression of miR-146a,and inhibit the proliferation,migration and invasion of GC cells through the PI3K/Akt pathway.

long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1microRNA146aproliferationphosphatidylinositol 3-kinase/protein kinase B pathwaymigrationinvasion

邢智伟、高紫玉、高雅楠、史雅瑄、刘彩霞

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内蒙古医科大学附属医院 肿瘤内科,内蒙古 呼和浩特 010050

内蒙古医科大学,内蒙古 呼和浩特 010107

长链非编码RNA肺腺癌转移相关转录子1 微小RNA146a 增殖 磷脂酰肌醇3激酶/蛋白激酶B通路 迁移 侵袭

内蒙古医科大学科技百万工程联合项目内蒙古医科大学致远人才计划

YKD2018KJBWLH013ZY0202030

2024

10.14066/j.cnki.cn21-1349/r.2022.0101

沈阳药科大学学报
沈阳药科大学

沈阳药科大学学报

CSTPCD
影响因子：0.604
ISSN：1006-2858
年,卷(期)：2024.41(5)
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