Background <p>MicroRNAs play key roles in tumor progression. miR-2116-5p is downregulated in lung adenocarcinoma (LUAD), and this study investigated its prognostic value and functional role in the disease.</p> Materials and methods <p>A total of 125 LUAD patients contributed tissue samples. miR-2116-5p and ADAM12 expression in tissues and cell lines were detected by RT‑qPCR. Clinicopathological correlations of miR-2116-5p were analyzed using the chi-square test. Kaplan‑Meier and Cox regression were employed to assess prognostic significance. CCK‑8, Transwell, and dual‑luciferase reporter assays were performed to investigate miR‑2116-5p function and its targeting of ADAM12. Rescue experiments validated the functional involvement of ADAM12.</p> Results <p>Significant downregulation of miR-2116-5p was observed in LUAD tissues and cell lines. Low expression was markedly linked to lymph node metastasis (<i>P</i> = 0.013) and advanced TNM stage (<i>P</i> = 0.002). Patients exhibiting reduced miR-2116-5p levels showed worse overall survival, and it was identified as an independent prognostic factor (HR = 2.521, 95% CI: 1.129–5.628, <i>P</i> = 0.020). Functional experiments showed that increasing miR-2116-5p expression suppressed LUAD cell proliferation, migration, and invasion, whereas its knockdown promoted these processes. ADAM12 was confirmed as a direct target, with expression inversely correlated in LUAD tissues (<i>r</i> = -0.749, <i>P</i> &lt; 0.001). ADAM12 overexpression effectively counteracted the ability of miR-2116-5p to suppress proliferation, migration, and invasion.</p> Conclusion <p>miR‑2116-5p suppresses LUAD progression by targeting ADAM12, suggesting it may serve as a prognostic biomarker and therapeutic target.</p>