lncRNA GAS5 targets miR-21 to inhibit epithelial-mesenchymal transformation and autophagy in lung cancer cells through the PI3K/Akt/mTOR signaling pathway
10.3969/j.issn.1673-4130.2025.05.012
- VernacularTitle:lncRNA GAS5靶向miR-21通过PI3K/Akt/mTOR信号通路抑制肺癌细胞的上皮-间质转化和自噬
- Author:
Qian ZHANG
1
;
Jie LIU
;
Hongxia MA
Author Information
1. 新疆医科大学附属中医医院呼吸与危重症医学科,新疆 乌鲁木齐 830002
- Keywords:
long non-coding RNA GAS5;
microRNA-21;
phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway;
lung cancer
- From:
International Journal of Laboratory Medicine
2025;46(5):568-574
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the inhibitory effect of long non-coding RNA(lncRNA)GAS5 on mi-croRNA-21(miR-21)in lung cancer cells through phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway on epithalium-mesenchymal transforma-tion and autophagy.Methods Real-time quantitative polymerase chain reaction(qPCR)was used to detect the expression of lncRNA GAS5 in 5 patients with non-small cell lung cancer(NSCLC)and adjacent groups.Dual luciferase reporter gene assay was used to detect the targeting effect of lncRNA GAS5 on miR-21.A549 cells were divided into 5 groups,including pcDNA-null group,pcDNA-GAS5 group,pcDNA-GAS5+mimic group,pcDNA-GAS5+mimic group and pcDNA-GAS5+mimic+BEZ235 group.lncRNA GAS5 and miR-21 expression were detected by qPCR.PI3K,phosphorylated Akt(p-Akt),phosphorylated mTOR(p-mTOR),Beclin1,microtubule-associated protein light chain 3(LC3)-Ⅱ,LC3-Ⅰ,E-cadherin,N-cadherin,Vimentin,Twist1,proliferation associated nuclear antigen(Ki67)and proliferating cell nuclear antigen(PCNA)expres-sion.The cell proliferation activity was measured by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide method.Results lncRNA GAS5 expression in NSCLC group was significantly higher than that in ad-jacent group,with statistical significance(P<0.05).Dual luciferase reporter gene assay determined that ln-cRNA GAS5 in A549 cells had a direct targeting effect on miR-21.Compared with pcDNA-null group,cell pro-liferation activity decreased in pcDNA-GAS5 group.lncRNA GAS5,PI3K,p-Akt,p-mTOR,Beclin1,LC3-Ⅱ,N-cadherin,Vimentin,Twist1,Ki67 and PCNA were down-regulated,while miR-21,LC3-Ⅰ and E-cadherin were up-regulated,the difference was statistically significant(P<0.05).Compared with pcDNA-GAS5+mimic group,the cell proliferation activity of pcDNA-GAS5+mimic group was up-regulated.The expressions of PI3K,p-Akt,p-mTOR,Beclin1,LC3-Ⅱ,N-cadherin,Vimentin,Twist1,Ki67,and PCNA were up-regulated,while the expressions of miR-21,LC3-Ⅰ,and E-cadherin were down-regulated,with statistical significance(P<0.05).Compared with pcDNA-GAS5+mimic group,the cell proliferation activity of pcDNA-GAS5+mimic+BEZ235 group was down-regulated.The expressions of PI3K,p-Akt,p-mTOR,Beclin1,LC3-Ⅱ,N-cadherin,Vimentin,Twist1,Ki67 and PCNA were down-regulated,while the expressions of LC3-Ⅰ and E-cad-herin were up-regulated,with statistical significance(P<0.05).Conclusion lncRNA GAS5 inhibits PI3K/Akt/mTOR signaling pathway through miR-21,thereby inhibiting epithelial-mesenchymal transformation and autophagy of lung cancer cells,and reducing cell proliferation activity.
