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

Issue:

2024 16

Page:

2959-2968

Research Field:

Publishing date:

Info

Title:

miR-34a inhibits the growth and metastasis of lung adenocarcinoma cells by blocking Wnt/¦Â-catenin signaling pathway to downregulate PD-L1 expression

Author(s):

LIU Xiaoqing; WANG Chunlou; ZHANG Xiaoling; XING Rongge; LIU Chunrong

Department of Pathology,Cangzhou Central Hospital Affiliated to Hebei Medical University,Hebei Cangzhou 061000,China.

Keywords:

immunotherapy; miR-34a; signaling pathways; molecular mechanisms

PACS:

R734.2

DOI:

10.3969/j.issn.1672-4992.2024.16.006

Abstract:

Objective:To study the effect and mechanism of miR-34a on proliferation,metastasis,and apoptosis of lung adenocarcinoma cells.Methods:105 lung adenocarcinoma patients were selected and divided into three groups based on their PD-L1 expression level (high,medium,low).Adenocarcinoma and adjacent tissues were collected,and miR-34a and Wnt signaling related gene mRNA and protein expression levels were detected using real-time fluorescence quantitative PCR (qRT-PCR) and Western blot (WB) methods.Construct miR-34a mimcs-pCMV,miR-34a inhibitor-pCMV vectors,and pCMV.Use liposomes to transfect lung adenocarcinoma A549 cells.CKK-8 assay was used to detect the proliferation activity of high expression,low expression,and negative control NC cells in miR-34a.Transwell cell assay,cell scratch assay,EdU assay were used to detect the invasion,migration and proliferation ability of each group of cells.The expression levels of PD-L1,Wnt signaling related genes,and lung adenocarcinoma related genes and proteins in each group of cells were detected by qPCR and WB methods.The targeted binding of miR-34a to Wnt1 and PD-L1 was detected by a dual luciferase system.Results:The expression of miR-34a was negatively correlated with the expression level of PD-L1 in the three groups of patients (P£¼0.05),while the expression level of Wnt signaling pathway related proteins was positively correlated with PD-L1 expression (P£¼0.05).Compared with the control NC group,the proliferation activity,migration ability,and invasion ability of cells in the miR-34a mimcs group were significantly reduced,while the proliferation,migration,and invasion ability of cells in the miR-34a inhibitor group were significantly increased (P£¼0.05).qPCR and WB results showed that the expression levels of PD-L1,Wnt pathway related proteins Wnt1,¦Â-catenin,GSK-3¦Â,PTEN,the expression of apoptosis-related protein Bcl-2,lung adenocarcinoma related driving genes EGFR,ROS1,ALK,and metastasis related genes MMP2,and Vimentin were significantly lower in the miR-34a mimcs group than in the miR-34a inhibitor group.The expression levels of Cleaved caspase-3 and p53 proteins related to cell apoptosis were significantly higher in the miR-34a mimcs group than in the miR-34a inhibitor group.The double luciferase reporter gene experiment verified that miR-34a can specifically bind to Wnt1 and PD-L1,and Wnt1 and PD-L1 were target genes regulated by miR-34a.Conclusion:miR-34a can inhibit the expression of PD-L1 protein and lung adenocarcinoma related driving genes,and inhibit the proliferation,migration,and invasion process of lung adenocarcinoma by regulating the Wnt1 protein to inhibit the Wnt/¦Â-catenin signaling pathway,simultaneously induce the expression of apoptosis related genes and promote apoptosis in lung adenocarcinoma cells.

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