LncRNA MAGI2-AS3通过靶向调控miR-1269a/PTEN/AKT通路增强非小细胞肺癌对顺铂化疗的敏感性

目的 研究lncRNA MAGI2-AS3对非小细胞肺癌顺铂耐药的影响及其分子机制.方法 采用qRT-PCR检测MAGI2-AS3和miR-1269a在顺铂敏感细胞(A549,H1299)和顺铂耐药细胞(A549/DDP,H1299/DDP)中的表达差异.采用慢病毒敲低A549和H1299中的MAGI2-AS3的表达,过表达A549/DDP和H1299/DDP中的MAGI2-AS3并加入20 μmol/L顺铂(DDP)处理.A549/DDP和H1299/DDP细胞实验分组为:OE-NC组,OE-MAGI2-AS3组,OE-NC+DDP组,OE-MAGI2-AS3+DDP组,A549和H1299...

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Published in南方医科大学学报 Vol. 44; no. 10; pp. 2033 - 2043
Main Authors 范喜瑞, 戚之琳, 邓园洁, 杨子晗, 孙丽, 李国豪, 梁娟娟, 吴菲, 袁力文
Format Journal Article
LanguageChinese
Published 皖南医学院 基础医学院生物化学与分子生物学教研室,安徽 芜湖 241002%皖南医学院 药学院,安徽 芜湖 241002%皖南医学院 临床医学院,安徽 芜湖 241002%皖南医学院 基础医学院生理学教研室,安徽 芜湖 241002%皖南医学院 检验学院,安徽 芜湖 241002%皖南医学院 麻醉学院,安徽 芜湖 241002 01.10.2024
Subjects
non-small cell lung cancer
LncRNA MAGI2-AS3
cisplatin resistance
miR-1269a
顺铂耐药
非小细胞肺癌
long noncoding RNA MAGI2-AS3
Online AccessGet full text
ISSN1673-4254
DOI10.12122/j.issn.1673-4254.2024.10.22

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Abstract 目的 研究lncRNA MAGI2-AS3对非小细胞肺癌顺铂耐药的影响及其分子机制.方法 采用qRT-PCR检测MAGI2-AS3和miR-1269a在顺铂敏感细胞(A549,H1299)和顺铂耐药细胞(A549/DDP,H1299/DDP)中的表达差异.采用慢病毒敲低A549和H1299中的MAGI2-AS3的表达,过表达A549/DDP和H1299/DDP中的MAGI2-AS3并加入20 μmol/L顺铂(DDP)处理.A549/DDP和H1299/DDP细胞实验分组为:OE-NC组,OE-MAGI2-AS3组,OE-NC+DDP组,OE-MAGI2-AS3+DDP组,A549和H1299细胞实验分组为:sh-NC组,sh-MAGI2-AS3组,sh-NC+DDP组,sh-MAGI2-AS3+DDP组.CCK-8和细胞克隆形成实验检测细胞存活率,流式细胞术和Western blotting分别检测细胞凋亡率和蛋白表达量,划痕实验和Transwell检测细胞EMT变化.通过网站GEPIA、StarBase和miRDB预测MAGI2-AS3、miR-1269a和PTEN之间的靶向关系,并采用荧光素酶报告基因实验和RIP实验验证.采用miR-1269a mimic和pcDNA3.1-PTEN进行Rescue实验.结果 MAGI2-AS3在肺癌组织中的表达显著低于正常癌旁组织(P<0.05)且与患者不良预后相关(P<0.05).A549/DDP和H1299/DDP中的MAGI2-AS3表达量显著低于A549和H1299(P<0.01).干扰MAGI2-AS3可以显著促进顺铂处理前、后A549和H1299细胞的存活及EMT进程(P<0.01),同时降低顺铂诱导的细胞凋亡(P<0.005).过表达MAGI2-AS3可以显著抑制顺铂处理前、后A549/DDP和H1299/DDP细胞存活与EMT进程(P<0.01),同时提升顺铂诱导的细胞凋亡(P<0.005).MAGI2-AS3与miR-1269a结合在一起,miR-1269a与PTEN 3'UTR结合.在A549/DDP细胞内MAGI2-AS3通过靶向吸附miR-1269a促进PTEN的表达并下调AKT磷酸化从而抑制顺铂刺激下细胞的EMT进程(P<0.01)、促进顺铂诱导的A549/DDP细胞凋亡(P<0.01).结论 LncRNA MAGI2-AS3通过靶向调控miR-
AbstractList 目的 研究lncRNA MAGI2-AS3对非小细胞肺癌顺铂耐药的影响及其分子机制.方法 采用qRT-PCR检测MAGI2-AS3和miR-1269a在顺铂敏感细胞(A549,H1299)和顺铂耐药细胞(A549/DDP,H1299/DDP)中的表达差异.采用慢病毒敲低A549和H1299中的MAGI2-AS3的表达,过表达A549/DDP和H1299/DDP中的MAGI2-AS3并加入20 μmol/L顺铂(DDP)处理.A549/DDP和H1299/DDP细胞实验分组为:OE-NC组,OE-MAGI2-AS3组,OE-NC+DDP组,OE-MAGI2-AS3+DDP组,A549和H1299细胞实验分组为:sh-NC组,sh-MAGI2-AS3组,sh-NC+DDP组,sh-MAGI2-AS3+DDP组.CCK-8和细胞克隆形成实验检测细胞存活率,流式细胞术和Western blotting分别检测细胞凋亡率和蛋白表达量,划痕实验和Transwell检测细胞EMT变化.通过网站GEPIA、StarBase和miRDB预测MAGI2-AS3、miR-1269a和PTEN之间的靶向关系,并采用荧光素酶报告基因实验和RIP实验验证.采用miR-1269a mimic和pcDNA3.1-PTEN进行Rescue实验.结果 MAGI2-AS3在肺癌组织中的表达显著低于正常癌旁组织(P<0.05)且与患者不良预后相关(P<0.05).A549/DDP和H1299/DDP中的MAGI2-AS3表达量显著低于A549和H1299(P<0.01).干扰MAGI2-AS3可以显著促进顺铂处理前、后A549和H1299细胞的存活及EMT进程(P<0.01),同时降低顺铂诱导的细胞凋亡(P<0.005).过表达MAGI2-AS3可以显著抑制顺铂处理前、后A549/DDP和H1299/DDP细胞存活与EMT进程(P<0.01),同时提升顺铂诱导的细胞凋亡(P<0.005).MAGI2-AS3与miR-1269a结合在一起,miR-1269a与PTEN 3'UTR结合.在A549/DDP细胞内MAGI2-AS3通过靶向吸附miR-1269a促进PTEN的表达并下调AKT磷酸化从而抑制顺铂刺激下细胞的EMT进程(P<0.01)、促进顺铂诱导的A549/DDP细胞凋亡(P<0.01).结论 LncRNA MAGI2-AS3通过靶向调控miR-
Abstract_FL Objective To investigate the mechanism mediating the regulatory effect of lncRNA MAGI2-AS3 on cisplatin(DDP)resistance in non-small cell lung cancer(NSCLC).Methods MAGI2-AS3 and miR-1269a expression levels were detected by qRT-PCR in DDP-sensitive lung cancer cell lines(A549 and H1299)and their resistant counterparts(A549/DDP and H1299/DDP).In A549 and H1299 cells with MAGI2-AS3 silencing and A549/DDP and H1299/DDP cells overexpressing MAGI2-AS3,the effects of 20 μmol/L DDP on cell viability and apoptosis were examined with CCK-8 assay,colony formation assay,flow cytometry and Western blotting,and the changes in epithelial-mesenchymal transition(EMT)were assessed with wound healing and Transwell assays.The interaction between MAGI2-AS3,miR-1269a and PTEN was predicted using GEPIA,StarBase and miRDB and verified with luciferase reporter gene assay and radioimmunoprecipitation(RIP)assay.A miR-1269a mimic and pcDNA3.1-PTEN plasmid were used to perform the rescue assay.Results MAGI2-AS3 expression was significantly downregulated in lung cancer tissues(P<0.05)in association with a poor prognosis(P<0.05).In the two DDP-resistant lung cancer cell lines,MAGI2-AS3 expression was significantly lowered as compared with the sensitive cells.Silencing MAGI2-AS3 significantly enhanced cell viability and promoted EMT of A549 and H1299 cells irrespective of DDP treatment,and also decreased DDP-induced apoptosis of the cells.In A549/DDP and H1299/DDP cells,MAGI2-AS3 overexpression strongly repressed cell viability and EMT irrespective of DDP treatment and promoted DDP-induced cell apoptosis.Luciferase reporter gene and RIP assays confirmed the binding of MAGI2-AS3 with miR-1269a and the binding of miR-1269a with 3'-UTR domain of PTEN.The rescue assay demonstrated that MAGI2-AS3 acted as a sponge for miR-1269a to promote PTEN expression and downregulate AKT phosphorylation,thus inhibiting EMT and promoting DDP-induced apoptosis of A549/DDP cells.Conclusion MAGI2-AS3 enhances DDP sensitivity of NSCLC by targeted regulation of the miR-1269a/PTEN/AKT signaling axis.
Author 杨子晗
梁娟娟
范喜瑞
吴菲
李国豪
袁力文
戚之琳
邓园洁
孙丽
AuthorAffiliation 皖南医学院 基础医学院生物化学与分子生物学教研室,安徽 芜湖 241002%皖南医学院 药学院,安徽 芜湖 241002%皖南医学院 临床医学院,安徽 芜湖 241002%皖南医学院 基础医学院生理学教研室,安徽 芜湖 241002%皖南医学院 检验学院,安徽 芜湖 241002%皖南医学院 麻醉学院,安徽 芜湖 241002
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Author_FL LI Guohao
LIANG Juanjuan
YUAN Liwen
FAN Xirui
SUN Li
DENG Yuanjie
YANG Zihan
WU Fei
QI Zhilin
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Keywords non-small cell lung cancer
LncRNA MAGI2-AS3
cisplatin resistance
miR-1269a
顺铂耐药
非小细胞肺癌
long noncoding RNA MAGI2-AS3
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Title LncRNA MAGI2-AS3通过靶向调控miR-1269a/PTEN/AKT通路增强非小细胞肺癌对顺铂化疗的敏感性
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