Marked dysregulation of mature 3p and 5p arms of miR-182 and miR-490 lacks prognostic value for 5-year survival in colorectal cancer

Abstract

Introduction: Colorectal cancer (CRC) is a leading cause of cancer mortality. MicroRNAs are key regulators of gene expression implicated in carcinogenesis. While miR-182 is an established oncomiR and miR-490 acts as a tumor suppressor, the prognostic significance of their mature arms (−3p/−5p) remains unclear. Objective: This study aims to validate these mature arms in CRC and assess their association with 5-year overall survival. Methods: We combined bioinformatics with experimental validation in 48 CRC patients. Putative targets were analyzed for their involvement in biological pathways. Expression levels were quantified in tumor and paired normal tissues using quantitative PCR. Associations with survival were evaluated using Kaplan–Meier and Cox proportional hazards models. Results: Bioinformatics linked miR-182 targets to cell movement and miR-490 to the mitotic cell cycle. In patient tissues, miR-182-5p (fold change [FC]: 16.19) and miR-182-3p (FC: 3.38) were significantly upregulated (p<0.05). Conversely, miR490-5p (FC: 0.26) and miR-490-3p (FC: 0.76) were significantly downregulated (p<0.05). Despite this dysregulation, multivariate Cox models showed no significant association with 5-year survival. Hazard ratios (HR) lacked significance for both miR182-5p (HR = 0.858, 95% CI: 0.610–1.205, p=0.377) and miR-490-3p (HR = 0.665, 95% CI: 0.357–1.239, p=0.198). Conclusion: This study validates the opposing dysregulation of mature miR-182 and miR-490 arms in CRC, reinforcing their respective oncogenic and tumor-suppressive roles. However, these profound expression changes did not translate into prognostic utility for 5-year survival in this cohort, suggesting that larger high-throughputbased studies are required to detect putative prognostic effects.