The Causal Relationship between Mirna and Colorectal Cancer: Result from Mendelian Randomization Study and RT-Qpcr Experiment Validation

Abstract

Background: Colorectal cancer (CRC) is a major global health concern, and understanding its molecular underpinnings is essential for effective intervention strategies. This study investigates the causal relationship between microRNAs (miRNAs) and CRC using a Mendelian Randomization (MR) approach, complemented by reverse transcription quantitative polymerase chain reaction (RT-qPCR) validation.

Methods: We conducted an extensive two-sample MR analysis. Briefly, the publicly available genetic data were utilized for investigation of the causal association between 2803 miRNAs and CRC; the inverse variance weighted (IVW) model and weighted medians were employed for MR analyses; and sensitivity analyses were adopted for heterogeneity and pleiotropy assessments and further confirm with RT-qPCR experiment.

Results: Our analysis revealed a total of 86 miRNAs associated with CRC. Of them, miR−4274 [odds ratio (OR) = 1.554, 95% confidence interval (CI) = 1.181– 2.044, p = 0.002], miR−4769−3p (OR = 1.357, 95% CI=1.120–1.644, p = 0.002), and miR−6789−5p (OR = 1.508, 95% CI=1.040– 2.187, p = 0.030) were strongly associated with CRC risks. The RT-qPCR results further confirmed that the expression levels of miR-4274, miR-4769-3p, and miR-6789-5p were significantly higher in CRC cell lines (HCT116, HT29, and Caco-2) compared with normal colon epithelial cells (HIEC).

Conclusion: These insights pave the way for further research into the clinical applications of miRNAs in CRC, offering promising avenues for diagnosis and treatment.