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Background <p>Lung adenocarcinoma (LUAD) is a subtype of lung cancer, which seriously endangers human life. Integrin subunit alpha 8 (ITGA8), a heterodimer transmembrane receptor protein, is closely related to the occurrence and development of tumors, but its research in LUAD is not very thorough.</p> Methods <p>In this study, a series of databases and bioinformatics tools were used to screen target genes and analyze their correlation with LUAD. The gene expression levels were detected by western blot and quantitative reverse transcription PCR (qRT-PCR). In the study of cell function, stable overexpression cell lines were constructed, and cell colony formation, proliferation, apoptosis, invasion, and migration were measured using clonal formation, 5-ethynyl-2’-deoxyuridine (EdU) staining, flow cytometry, transwell, and wound healing assays, respectively. Moreover, bioinformatics methods, Ki-67 staining, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining were put to use for assessing the association between ITGA8 and immune escape. In terms of mechanism, the binding sites between transcription factor 21 (TCF21) and ITGA8 promoters were predicted adopting the&#xa0;GSE87410 and hTFtarget&#xa0;databases. Moreover, the combination of ITGA8 and TCF21 were validated by chromatin immunoprecipitation (ChIP)-qPCR and dual-luciferase reporter assay. In vivo, xenograft mouse models were used to verify the relationship between ITGA8 and TCF21 in tumor growth of LUAD.</p> Results <p>Compared with the&#xa0;normal groups, ITGA8 expression was reduced in the&#xa0;LUAD groups, which was associated with a poorer prognosis&#xa0;of patients. ITGA8 suppressed the colony formation, proliferation, invasion, and migration of LUAD cell lines, and promoted apoptosis. Meanwhile, ITGA8 restrained the immune escape of CD8<sup>+</sup> T cells. Mechanically, TCF21 participated in the LUAD occurrence by activating the transcription of ITGA8. In vivo, ITGA8 restrained tumor growth through the same mechanism.</p> Conclusion <p>TCF21 impedes LUAD progression and immune escape through the&#xa0;transcriptional regulation of ITGA8. This will provide a new target for the therapy of LUAD.</p>

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TCF21 mediates ITGA8 to block LUAD progression and immune escape

  • 期刊论文

  • 发表日期：

    2025年6月26日

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  • Lei Zhu,
  • Qian Yang,
  • Shirui Ding,
  • Tao Song,
  • Yangzhen Zhou

摘要

Background

Lung adenocarcinoma (LUAD) is a subtype of lung cancer, which seriously endangers human life. Integrin subunit alpha 8 (ITGA8), a heterodimer transmembrane receptor protein, is closely related to the occurrence and development of tumors, but its research in LUAD is not very thorough.

Methods

In this study, a series of databases and bioinformatics tools were used to screen target genes and analyze their correlation with LUAD. The gene expression levels were detected by western blot and quantitative reverse transcription PCR (qRT-PCR). In the study of cell function, stable overexpression cell lines were constructed, and cell colony formation, proliferation, apoptosis, invasion, and migration were measured using clonal formation, 5-ethynyl-2’-deoxyuridine (EdU) staining, flow cytometry, transwell, and wound healing assays, respectively. Moreover, bioinformatics methods, Ki-67 staining, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining were put to use for assessing the association between ITGA8 and immune escape. In terms of mechanism, the binding sites between transcription factor 21 (TCF21) and ITGA8 promoters were predicted adopting the GSE87410 and hTFtarget databases. Moreover, the combination of ITGA8 and TCF21 were validated by chromatin immunoprecipitation (ChIP)-qPCR and dual-luciferase reporter assay. In vivo, xenograft mouse models were used to verify the relationship between ITGA8 and TCF21 in tumor growth of LUAD.

Results

Compared with the normal groups, ITGA8 expression was reduced in the LUAD groups, which was associated with a poorer prognosis of patients. ITGA8 suppressed the colony formation, proliferation, invasion, and migration of LUAD cell lines, and promoted apoptosis. Meanwhile, ITGA8 restrained the immune escape of CD8+ T cells. Mechanically, TCF21 participated in the LUAD occurrence by activating the transcription of ITGA8. In vivo, ITGA8 restrained tumor growth through the same mechanism.

Conclusion

TCF21 impedes LUAD progression and immune escape through the transcriptional regulation of ITGA8. This will provide a new target for the therapy of LUAD.