|Table of Contents|

Up-regulation of HHLA2 induced by c-Jun promotes the proliferation,migration and invasion of EGFR mutant lung adenocarcinoma

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2025 06
Page:
924-931
Research Field:
Publishing date:

Info

Title:
Up-regulation of HHLA2 induced by c-Jun promotes the proliferation,migration and invasion of EGFR mutant lung adenocarcinoma
Author(s):
LIU Xin1; 2; LI Yan1; 2; MAO Zhiyuan2; WANG Lihong2 ; YU Haiyan2; SUN Li2; LIU Juqin2; SUN Lulu2; FAN Zaiwen2
1.Graduate School of Hebei North University,Hebei Zhangjiakou 075000,China;2.Department of Oncology,Air Force Medical Center,Beijing 100142,China.
Keywords:
HHLA2; c-Jun; lung adenocarcinoma; EGFR mutations
PACS:
R734.2
DOI:
10.3969/j.issn.1672-4992.2025.06.006
Abstract:
Objective:To investigate the effect of c-Jun-induced up-regulation of HHLA2 on the occurrence and development of EGFR-mutant lung adenocarcinoma.Methods:The differential expression and clinical features of HHLA2 between EGFR mutant and wild type were analyzed,and the possible signaling pathways were involved.The transcription factors regulating HHLA2 were predicted.EGFR wild type lung adenocarcinoma cell line A549 and EGFR mutant lung adenocarcinoma cell line H1975 were used to construct transient plasmid c-Jun overexpression cell lines A549-c-Jun and H1975-c-Jun.The cells were divided into 4 groups:Group a (A549-c-Jun),group b (A549+empty vector),group c (H1975-c-Jun),group d (H1975+empty vector).Dual luciferase reporter assay was used to verify the interaction between transcription factor c-Jun and HHLA2.Cell counting kit-8 (CCK-8),Transwell and cell scratch assay were used to detect the proliferation,migration and invasion of each group before and after c-Jun overexpression.qRT-PCR was used to detect the expression of HHLA2 mRNA.The expression of HHLA2 protein was detected by Western blot.Results：The expression of HHLA2 in LUAD tissues with EGFR mutation was significantly higher than that with EGFR wild type (P＜0.05).The overall survival of LUAD patients with high HHLA2 expression was significantly shortened (P＜0.05).T stage and HHLA2 expression were related to the prognosis of patients.Dual luciferase reporter assay showed that the fluorescence intensity of c-Jun overexpressed cell lines was significantly increased (P＜0.05).Overexpression of c-Jun significantly enhanced the migration,proliferation and invasion of EGFR-mutant lung adenocarcinoma cells (P＜0.05).The expression level of HHLA2 was increased in EGFR-mutant lung adenocarcinoma cell lines (P＜0.05).Conclusion:c-Jun-induced up-regulation of HHLA2 promotes the proliferation,migration,invasion and other biological behaviors of EGFR-mutant lung adenocarcinoma cells,and promotes the occurrence and development of lung adenocarcinoma.

References:

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