Circ-FOXM1 knockdown suppresses non-small cell lung cancer development by regulating the miR-149-5p/ATG5 axis

Area of Science:

• Oncology
• Molecular Biology
• Genetics

Background:

• Circular RNAs (circRNAs) are implicated in human cancer development.
• The specific role of circ-FOXM1 in non-small cell lung cancer (NSCLC) progression remained largely unelucidated.
• Understanding the functional mechanisms of circRNAs is crucial for cancer research.

Purpose of the Study:

• To investigate the role and functional mechanism of circ-FOXM1 in NSCLC.
• To explore the relationship between circ-FOXM1, microRNA-149-5p (miR-149-5p), and autophagy-related 5 (ATG5) in NSCLC.
• To determine if circ-FOXM1 could serve as a therapeutic target for NSCLC.

Main Methods:

• Quantitative real-time polymerase chain reaction (RT-qPCR) to measure gene expression.
• Cell Counting Kit-8 (CCK-8), flow cytometry, and transwell assays for cellular analysis.
• Western blot for protein expression, and mouse xenograft models for in vivo studies.
• Bioinformatic prediction (Starbase3.0) and experimental validation (dual-luciferase reporter and RNA pull-down assays) for molecular interactions.

Main Results:

• Circ-FOXM1 and ATG5 were upregulated, while miR-149-5p was downregulated in NSCLC tissues and cells.
• Circ-FOXM1 knockdown significantly suppressed NSCLC cell viability, migration, and autophagy, while inducing apoptosis.
• Circ-FOXM1 directly targets miR-149-5p, leading to the upregulation of ATG5; miR-149-5p inhibits ATG5 expression.

Conclusions:

• Circ-FOXM1 promotes NSCLC progression by modulating the miR-149-5p/ATG5 axis.
• Circ-FOXM1 knockdown attenuates NSCLC development, suggesting its potential as a therapeutic target.
• The findings provide a theoretical basis for developing novel therapies for NSCLC targeting the circ-FOXM1/miR-149-5p/ATG5 pathway.