circFOXK2 inhibits vascular permeability and angiogenesis in advanced lung adenocarcinoma via the miR-1275/CLDN1 axis

Area of Science:

• Oncology
• Molecular Biology
• Vascular Biology

Background:

• CircRNAs regulate angiogenesis, but their function in advanced lung adenocarcinoma (LUAD) is not well understood.
• Angiogenesis is critical for tumor growth and metastasis in LUAD.

Purpose of the Study:

• To investigate the role of circFOXK2 in LUAD angiogenesis.
• To elucidate the molecular mechanisms by which circFOXK2 influences angiogenesis.
• To explore the therapeutic potential of targeting the circFOXK2/miR-1275/CLDN1 axis in LUAD.

Main Methods:

• Analysis of circFOXK2 expression in LUAD tissues and correlation with clinical outcomes.
• In vitro and in vivo experiments to study the effects of circFOXK2, miR-1275, and CLDN1 on endothelial cells and angiogenesis.
• Exosome isolation and characterization.
• Combination therapy studies with circFOXK2 and bevacizumab.

Main Results:

• circFOXK2 expression was significantly decreased in advanced LUAD with high angiogenic activity, correlating with poor prognosis.
• Reduced circFOXK2 led to increased miR-1275 in tumor-derived exosomes, which were internalized by endothelial cells.
• miR-1275 overexpression silenced CLDN1 in endothelial cells, increasing vascular permeability and promoting angiogenesis.
• Combination of circFOXK2 overexpression and bevacizumab demonstrated a synergistic anti-angiogenic effect.

Conclusions:

• The circFOXK2/miR-1275/CLDN1 axis is a key regulator of vascular permeability and angiogenesis in advanced LUAD.
• This axis represents a promising therapeutic target for LUAD treatment.
• Restoring circFOXK2 function, potentially in combination with anti-angiogenic drugs like bevacizumab, offers a novel therapeutic strategy.