MicroRNA-124-3p suppresses lung cancer by targeting ITGB1/PI3K/p-AKT signal transduction pathway

Area of Science:

• Molecular Oncology
• Cancer Biology
• Gene Regulation

Background:

• Non-small cell lung cancer (NSCLC) is a leading cause of cancer mortality worldwide.
• MicroRNAs (miRNAs) are crucial regulators in NSCLC pathogenesis.
• MicroRNA-124-3p (miR-124-3p) is implicated as a tumor-associated miRNA with confirmed downregulation in NSCLC.

Purpose of the Study:

• To investigate the role of miR-124-3p in NSCLC progression.
• To identify the molecular targets and signaling pathways regulated by miR-124-3p.
• To evaluate the therapeutic potential of miR-124-3p in NSCLC.

Main Methods:

• Functional assays (overexpression and knockdown) to assess NSCLC cell proliferation and migration.
• Luciferase reporter assay to validate direct targeting of ITGB1 by miR-124-3p.
• Western blotting to analyze PI3K/AKT signaling pathway activation.
• Bioinformatics analysis of miRNA expression in tumor tissues versus normal lung tissues and correlation with clinical staging.

Main Results:

• Overexpression of miR-124-3p suppressed NSCLC cell proliferation and migration, while knockdown promoted these phenotypes.
• miR-124-3p directly targets the 3'-UTR of ITGB1.
• ITGB1 activates the PI3K/AKT pathway by enhancing PI3K expression and AKT phosphorylation.
• miR-124-3p demonstrated tumor-suppressive effects even in cells with PIK3CA mutations.
• Bioinformatics analysis revealed decreased miR-124-3p expression in NSCLC tissues, correlating with advanced tumor stage.

Conclusions:

• miR-124-3p acts as a tumor suppressor in NSCLC by inhibiting progression through the ITGB1/PI3K/p-AKT axis.
• The tumor-suppressive function of miR-124-3p is maintained despite PIK3CA activation.
• miR-124-3p represents a promising therapeutic candidate for NSCLC treatment.