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GATA6 Suppresses Lung Adenocarcinoma Progression by Activating CFTR to Modulate Arachidonic Acid Metabolism.
Lin, Yong; Chen, Yushan; Zhang, Yi; Weng, Jianming; Shen, Rongqiang; Zhang, Wenshan; Lin, Yulin.
Afiliación
  • Lin Y; Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
  • Chen Y; Department of Radiology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
  • Zhang Y; Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
  • Weng J; Department of Pathology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
  • Shen R; Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
  • Zhang W; Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
  • Lin Y; Department of Cardiothoracic Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, 363000, China.
Comb Chem High Throughput Screen ; 2024 Jan 30.
Article en En | MEDLINE | ID: mdl-38299406
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 via 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Comb Chem High Throughput Screen Asunto de la revista: BIOLOGIA MOLECULAR / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Emiratos Árabes Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Comb Chem High Throughput Screen Asunto de la revista: BIOLOGIA MOLECULAR / QUIMICA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Emiratos Árabes Unidos