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

Worldwide, lung cancer is a leading cause of cancer-related death, and non-small cell lung cancer (NSCLC) represents the most common histological subtype. Numerous studies have demonstrated that microRNAs (miRNAs) play critical roles in NSCLC pathogenesis. microRNA-124-3p (miR-124-3p) has been identified as a tumor-associated miRNA, and we confirmed its downregulation in NSCLC cells. Functional assays showed that overexpression of miR-124-3p suppresses proliferation and migration of NSCLC cells, whereas its knockdown promotes these malignant phenotypes. A luciferase reporter assay revealed that miR-124-3p directly targets ITGB1 by binding to its 3'-UTR. Mechanistically, ITGB1 enhances PI3K expression and increases AKT phosphorylation, thereby activating the PI3K/AKT signaling pathway. Notably, miR-124-3p retained its tumor-suppressive effects even in A549 cells engineered to express the PIK3CAH1047L mutation. Consistent with this, bioinformatics analysis demonstrated that miR-124-3p expression is significantly lower in tumor tissues than in adjacent normal lung and further decreases in advanced T stage (T3-T4) compared to early stage (T1-T2). These findings indicate that miR-124-3p inhibits NSCLC progression via the ITGB1/PI3K/p-AKT axis and remains functional despite PIK3CA activation, supporting its potential as a therapeutic candidate.