High expression of LINC00467 promotes proliferation and metastasis of lung adenocarcinoma cells by suppressing autophagy via inhibiting the AMPK/mTOR pathway
10.12122/j.issn.1673-4254.2024.10.08
- VernacularTitle:LINC00467高表达通过抑制AMPK/mTOR通路抑制细胞自噬促进肺腺癌细胞的增殖和转移
- Author:
Yonghua LI
1
;
Xinran XI
;
Meng ZHANG
;
Xun WU
;
Xianghai WANG
Author Information
1. 皖南医学院第一附属医院//弋矶山医院呼吸内科,安徽 芜湖 241001
- Keywords:
LINC00467;
lung adenocarcinoma;
autophagy;
proliferation;
metastasis;
AMPK/mTOR signaling pathway
- From:
Journal of Southern Medical University
2024;44(10):1898-1909
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the regulatory effects of LINC00467 on proliferation and metastasis of lung adenocarcinoma cells and the involvement of autophagy in its regulatory mechanism.Methods LINC00467 expression levels in lung adenocarcinoma tissues and their correlation with the patients'survival outcomes were analyzed using data from TCGA database.LINC00467 expression was also examined using qRT-PCR in human bronchial epithelial cells 16HBE and lung adenocarcinoma cell lines A549 and H1299.In A549 and H1299 cells transfected with a short hairpin RNA targeting LINC00467(shLINC00467),the effects of 3-methyladenine(3-MA,an autophagy inhibitor)and BML-275(an AMPK inhibitor)treatment on cell proliferation,migration,and expressions of LC3 and the AMPK/mTOR pathway proteins were tested using colony formation assay,wound-healing and Transwell assays,immunofluorescence staining and Western blotting.GSEA enrichment analysis was conducted to analyze the correlation between LINC00467 and the autophagy pathway.Results The expression level of LINC00467 was significantly higher in lung adenocarcinoma tissues than in the adjacent tissues(P<0.001)and increased progressively with the clinical stage(P<0.05),and its high expression was associated with a poor overall survival(P=0.049)and a high first progression rate(P=0.026)of the patients.LINC00467 expression was also significantly higher in A549 and H1299 cells than in 16HBE cells.In A549 and H1299 cells,LINC00467 knockdown significantly decreased colony-forming,migration and invasion abilities of the cells,lowered p-mTOR/mTOR and p62 expressions,and increased p-AMPK/AMPK expressions and LC3Ⅱ/Ⅰ ratio,and these effects were strongly attenuated by application of either 3-MA or BML-275.GSEA analysis suggested an inhibitory effect on LINC00467 on the autophagy pathway(|NES|>1,P<0.05,FDR<0.25).Conclusion High expressions of LINC00467 promote proliferation and metastasis of lung adenocarcinoma cells possibly by inhibiting cell autophagy mediated by the AMPK/mTOR signaling pathway.
