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Updated: Jan 16, 2026
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Investigating the relationship of plasma microRNAs and colorectal cancer risk using genetic evidence
Emmanouil Bouras1,2, Christos K Papagiannopoulos3, Rima Mustafa4,5
1Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, White City Campus, 90 Wood Lane, London, W12 0BZ, UK. ebouras@ic.ac.uk.
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.
Insights
Five microRNAs (miRNAs) show potential links to colorectal cancer (CRC) risk. Further research is needed to understand their downstream effects for potential prevention strategies.
Area of Science:
- Genetics and Molecular Biology
- Cancer Research
- Biomarkers
Background:
- MicroRNAs (miRNAs) are key post-transcriptional gene regulators.
- Circulating miRNAs are implicated in carcinogenesis.
- Systematic investigation of miRNAs in relation to colorectal cancer (CRC) risk is lacking.
Purpose of the Study:
- To investigate the association between genetically predicted plasma miRNA concentrations and CRC risk.
- To explore potential downstream molecular pathways and protein associations of identified miRNAs.
- To assess the role of specific miRNAs in CRC development.
Main Methods:
- Mendelian randomization (MR) and colocalization analyses were employed.
- Investigated 2083 plasma miRNAs for association with CRC risk in a large cohort.
- MR was used to examine associations with circulating plasma proteins and pathway enrichment analysis (PEA) was performed.
Main Results:
- Five miRNAs (miR-146a-5p, miR-21-5p, miR-4707-3p, miR-1908-5p, miR-6810-3p) showed significant associations with CRC risk.
- miR-146a-5p, miR-21-5p, and miR-4707-3p were positively associated; miR-1908-5p and miR-6810-3p were inversely associated.
- Identified protein associations and 11 pathways, including Erb-B2 receptor tyrosine kinase and insulin-like growth factor pathways.
Conclusions:
- The study supports a potential role for five specific miRNAs in CRC risk.
- Further elucidation of downstream effects is necessary.
- These miRNAs may represent future preventive targets for colorectal cancer.
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