PLAU, transcriptionally negatively regulated by GATA6, promotes lung squamous carcinoma cell proliferation and...

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Lung squamous cell carcinoma (LUSC) presents a significant mortality challenge with limited treatment options.
• Plasminogen activator urokinase (PLAU) is implicated in tumor malignancy, but its specific role in LUSC progression is unclear.
• GATA-binding factor 6 (GATA6) regulates lung development and inhibits LUSC cell growth, yet its regulatory mechanisms, particularly concerning PLAU, require further investigation.

Purpose of the Study:

• To elucidate the oncogenic role of PLAU in LUSC development and progression.
• To investigate the transcriptional regulatory mechanism of GATA6 on PLAU expression in LUSC.
• To identify potential therapeutic targets within the GATA6/PLAU pathway for LUSC treatment.

Main Methods:

• Differential gene expression analysis (GEO datasets, RNA-seq) and Venn analysis identified potential GATA6 targets.
• Real-time PCR, immunoblotting, and dual-luciferase reporter assays confirmed GATA6's transcriptional regulation of PLAU.
• Cell proliferation (EdU), 3D culture, migration (Transwell), and immunohistochemistry assays assessed PLAU's function and expression in LUSC tissues.

Main Results:

• PLAU overexpression significantly enhanced LUSC cell proliferation and migration.
• PLAU was found to be overexpressed in LUSC tissues compared to normal tissues.
• High PLAU expression independently predicted poor prognosis in LUSC patients and is transcriptionally regulated by GATA6.

Conclusions:

• PLAU acts as a novel oncogene in LUSC, promoting tumor progression.
• A new molecular mechanism involving GATA6's transcriptional inhibition of PLAU in LUSC was identified.
• Targeting the GATA6/PLAU pathway presents a promising strategy for developing novel LUSC therapeutics.