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Introduction: Our previous study found that miR-145 was downregulated in non-small cell lung cancer (NSCLC) tissues and it could inhibit cell proliferation in transfected NSCLC cells. This study aimed to investigate the potential anticancer effect and tumor suppressive function of miR-145, to identify its gene targets, as well as to assess the role of its gene targets as prognostic biomarkers for NSCLC patients. Materials and Methods: Cell proliferation, transwell migration, and invasion assays were performed on three miR-145 mimics transfected NSCLC cells. The effect of miR-145 in the cell cycle in vitro was assessed by flow cytometry analysis. In vivo transfection of miR-145 was performed to examine the cancer growth in eight BALB/c nude mice. Luciferase reporter assay was used to identify the gene targets. To reveal the role of the identified gene targets in patient survival, the clinical data of 500 lung adenocarcinoma patients from The Cancer Genome Atlas (TCGA) database was used for Kaplan-Meier survival analysis. Results: Upregulation of miR-145 significantly inhibited proliferation, migration, and invasion in NSCLC cells in vitro. Flow cytometry analysis revealed that the transfection of miR-145 into NSCLC cells did not show any effect in the cell cycle. After 37 days, transfection of miR-145 showed a reduction in tumor size (49% smaller) and tumor weight (57% lighter) than mimic negative in vivo. MicroRNA target prediction database miRTarBase and luciferase reporter assays identified GOLM1 and RTKN as the direct targets of miR-145. TCGA survival analysis found that the high expressions of GOLM1 (p < 0.0001) and RTKN (p < 0.0045) were significantly correlated with poor overall survival in lung adenocarcinoma patients. Conclusion: Our results revealed that miR-145 inhibited proliferation, migration, and invasion, but did not affect cell cycle regulation in NSCLC. It also caused a reduction in tumor growth and weight. Most importantly, we identified two direct targets (GOLM1 and RTKN) of miR-145, in which RTKN was first identified as a miR-145 target in NSCLC. Moreover, both GOLM1 and RTKN play an imperative role in patients’ overall survival. Taken together, our findings suggest that miR-145 may serve as a molecular therapeutic target for NSCLC, and its gene targets GOLM1 and RTKN may serve as prognostic biomarkers. Their potential clinical applications warrant further investigation. Citation Format: William C. Cho, Chi F. Wong, Leo K. Li, Alvin H. Fong. miR-145 and its gene targets as therapeutic target and prognostic biomarkers for non-small cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3756.