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Volume 28, Issue 4
  • ISSN: 1386-2073
  • E-ISSN: 1875-5402

Abstract

Background

CFTR, which belongs to the ATP-binding cassette transporter family and whose members are always involved in cancer progression, is implicated in lung adenocarcinoma (LUAD) progression, but the underlying mechanism remains undefined. Therefore, this study intended to investigate how CFTR works exactly on LUAD progression.

Methods

Bioinformatics methods were utilized to analyze GATA6 and CFTR expression in LUAD and targeting relationship, followed by a pathway enrichment analysis of CFTR. GATA6 and CFTR expression levels were assessed by qRT-PCR. Cell viability and proliferation were detected through MTT and colony formation assays. An arachidonic acid (AA) assay kit was utilized to measure AA content. mRNA and protein expression levels of genes (cPLA2, COX-2, and CYP1A1) related to the AA metabolism pathway were detected by qRT-PCR and western blot, respectively. Moreover, the Dual-luciferase reporter gene assay and ChIP were used to verify the binding of GATA6 and CFTR promoters.

Results

GATA6 and CFTR were lowly expressed in LUAD, and CFTR was enriched in the AA metabolism pathway. GATA6 activated CFTR transcription. Cellular and rescue experiments revealed that low or high CFTR expression could foster or hamper LUAD cell viability and proliferation, and concomitant treatment of indomethacin, an AA metabolism pathway inhibitor, mitigated stimulation on LUAD progression by low CFTR expression. Silencing of GATA6 reversed the suppressive impact of CFTR overexpression on LUAD progression modulation of the AA metabolism pathway.

Conclusion

The activation of CFTR by GATA6 hampered LUAD progression by modulating the AA metabolism pathway, suggesting that GATA6/CFTR axis might be a therapeutic target for LUAD patients.

© 2025 Bentham Science Publishers
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2024-01-30
2025-03-29

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/content/journals/cchts/10.2174/0113862073269158240122072743
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GATA6 Suppresses Lung Adenocarcinoma Progression by Activating CFTR to Modulate Arachidonic Acid Metabolism
Comb Chem High Throughput Screen 28, 582 (2025); https://doi.org/10.2174/0113862073269158240122072743
/content/journals/cchts/10.2174/0113862073269158240122072743
/content/journals/cchts/10.2174/0113862073269158240122072743
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  • Article Type:     Research Article
Keyword(s): arachidonic acid; CFTR; CFTR promoters; GATA6; lung adenocarcinoma; mRNA

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