AmitisGen TECH Dev Group Personalized and Precision Medicine Journal 3115-7874 11 41 2026 06 30 Circulating miR-21-5p as a Diagnostic Biomarker in Colorectal Cancer: Clinical Evaluation and Integrated Bioinformatics Analysis of Its Molecular Targets 54 63 738541 10.22034/ppmj.2026.738541 EN Farnoosh Honarmand Department of Biology, Faculty of Basic Sciences, Tehran Branch, University of Science and Culture, Tehran, Iran. Mahnaz Saremi Reference Health Laboratory, Ministry of Health and Medical Education, Tehran, Iran. Journal Article 2026 02 17 Background: Circulating microRNAs have emerged as promising minimally invasive biomarkers for colorectal cancer (CRC). This study evaluated the expression and diagnostic performance of circulating hsa-miR-21-5p and investigated its potential molecular targets using integrated bioinformatics analysis.<br>Methods: Plasma samples were obtained from 50 treatment-naïve male patients with histologically confirmed grade II CRC and 20 healthy male controls. Circulating RNA was extracted and miR-21-5p expression was quantified using stem-loop reverse transcription quantitative PCR. Hsa-miR-1228-3p was used as the endogenous reference, and relative expression was calculated using the 2^−ΔΔCq method. Diagnostic performance was assessed by receiver operating characteristic analysis. High-confidence target genes were identified using miRDB and TargetScan, followed by protein–protein interaction analysis using STRING.<br>Results: The mean ages of patients and controls were 55 and 49 years, respectively, with no significant between-group difference (P=0.162). Circulating miR-21-5p expression was significantly higher in CRC patients than in healthy controls (P=0.002). ROC analysis yielded an area under the curve of 0.873 (95% CI, 0.766–0.979; P<0.0001). Target prediction identified a set of high-confidence genes involved in cell proliferation, apoptosis, immune regulation, adhesion, extracellular-matrix organization, and transcriptional control. STRING analysis revealed a functionally connected network containing central signaling proteins, including STAT3, YAP1, SKP2, PDCD4, TRAF6, and SPRY-family proteins.<br>Conclusion: Circulating miR-21-5p demonstrated good ability to distinguish CRC patients from healthy controls. The bioinformatics findings suggest that its biological effects may involve interconnected oncogenic, apoptotic, immune, and invasion-related pathways. https://www.pmjournal.ir/article_738541_54805fcc3e9cf7760f1fc9334c3be4dc.pdf