Investigating the relationship of plasma microRNAs and colorectal cancer risk using genetic evidence
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: MicroRNAs (miRNAs) are short, single-stranded RNAs that function as post-transcriptional regulators of gene expression. Although circulating miRNAs have been linked to carcinogenesis, they have not yet been systematically investigated in relation to risk of colorectal cancer (CRC). METHODS: We used Mendelian randomization (MR) and colocalization analyses to investigate the association of genetically predicted plasma miRNA concentrations (2083 miRNAs in 710 individuals) with risk of CRC (58,221 cases and 67,694 controls). For miRNAs associated with CRC risk, we also investigated their association with circulating plasma proteins (4907 proteins in 35,559 participants), bidirectionally, using MR. We performed pathway enrichment analysis (PEA) to explore downstream molecular pathways. RESULTS: Associations of five miRNAs with CRC were found in MR and supported in colocalization analyses. Specifically, miR-146a-5p, miR-21-5p, and miR-4707-3p were positively, and miR-1908-5p and miR-6810-3p were inversely associated with CRC risk. Several protein associations were found for these miRNAs (range of proteins with P < 0.05: 78-796; 211 with FDR < 5%), and 11 pathways were identified in PEA, including regulation of Erb-B2 receptor tyrosine kinase 4 (miR-6810-3p) and insulin-like growth factor pathways (miR-1908-5p). CONCLUSIONS: Our results support a potential implication of miR-146a-5p, miR-21-5p, miR-4707-3p, miR-1908-5p, and miR-6810-3p to CRC risk. However, their downstream effects should be elucidated before they can be utilized as preventive targets.
Source: BMC Medicine
Authors: Emmanouil Bouras, Christos K. Papagiannopoulos, Rima Mustafa, Daniel Sobieski, Stephanie L. Schmit, Anna H. Wu, Hermann Brenner, Christopher I. Li, Andrew T. Chan, Andrew J. Pellatt, Wei Zheng, Temitope O. Keku, Victor Moreno, Caroline Y. Um, Bethany Van Guelpen, Amanda I. Phipps, Rish K. Pai, Sarah J. Lewis, Richard M. Martin, Marc J. Gunter, Ulrike Peters, Abbas Dehghan, Konstantinos K. Tsilidis
Institutions: University of Ioannina, Imperial College London, University of Oxford, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine, University of Southern California, German Cancer Research Center, Deutsches Konsortium für Translationale Krebsforschung, Fred Hutch Cancer Center, Broad Institute, Brigham and Women's Hospital, Harvard University, Massachusetts General Hospital, Intermountain Healthcare, Vanderbilt University, Vanderbilt-Ingram Cancer Center, University of North Carolina at Chapel Hill, Institut Català d'Oncologia, American Cancer Society, Umeå University, University of Washington, Mayo Clinic in Arizona, University of Bristol, NIHR Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust, Centre international de recherche sur le cancer
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
OpenAlex ID: W4414752040