Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer and remains a leading cause of cancer-related mortality worldwide. MicroRNAs (miRNAs) are critical regulators of tumor progression; however, the biological role and molecular mechanisms of miR-589-3p in LUAD remain unclear. In this study, the expression levels of miR-589-3p and WWC2 were analyzed using The Cancer Genome Atlas lung adenocarcinoma (TCGA-LUAD) datasets via the UALCAN platform. Flow cytometric apoptosis analysis and functional assays including CCK-8, colony formation, AO/EB staining, and Transwell invasion assays were performed in LUAD cell lines. The interaction between miR-589-3p and WWC2 was validated using dual-luciferase reporter assays, Western blotting, and rescue experiments. miR-589-3p expression was significantly elevated in LUAD tissues compared with normal lung tissues (p < 0.05) and was positively associated with an advanced tumor stage and lymph node metastasis (p < 0.05). Inhibition of miR-589-3p significantly suppressed proliferation and colony formation (p < 0.05), reduced invasive capacity (p < 0.05), and markedly increased apoptosis (p < 0.01) in LUAD cells. Dual-luciferase reporter assays confirmed WWC2 as a direct target of miR-589-3p, with miR-589-3p mimics significantly reducing WWC2 wild-type reporter activity (p < 0.05). WWC2 expression was significantly downregulated in LUAD tissues (p < 0.05), and WWC2 knockdown reversed the anti-proliferative, pro-apoptotic, and anti-invasive effects induced by miR-589-3p inhibition (p < 0.01). These findings demonstrate that miR-589-3p promotes lung adenocarcinoma progression by directly suppressing WWC2. The miR-589-3p/WWC2 axis represents a novel molecular mechanism contributing to LUAD malignancy and may provide a foundation for future mechanistic and translational studies.
Sultan F. Kadasah (Thu,) studied this question.