miRNA involvement in cell cycle regulation in colorectal cancer cases

Abstract

Uncontrolled cell replication is a key component of carcinogenesis. MicroRNAs (miRNAs) regulate genes involved in checkpoints, DNA repair, and genes encoding for key proteins regulating the cell cycle. We investigated how miRNAs and mRNAs in colorectal cancer subjects interact to regulate the cell cycle. Using RNA-Seq data from 217 individuals, we analyzed differential expression (carcinoma minus normal mucosa) of 123 genes within the cell cycle pathway with differential miRNA expression, adjusting for age and sex. Multiple comparison adjustments for gene/miRNA associations were made at the gene level using an FDR <0.05. Differentially expressed miRNAs and mRNAs were tested for associations with colorectal cancer survival. MRNA and miRNA sequences were compared to identify seed region matches to support biological interpretation of the observed associations. Sixty-seven mRNAs were dysregulated with a fold change (FC) <0.67 or >1.50. Thirty-two mRNAs were associated with 48 miRNAs; 102 of 290 total associations had identified seed matches; of these, ten had negative beta coefficients. Hsa-miR- 15a-5p and hsa-miR-20b-5p were associated with colorectal cancer survival with an FDR <0.05 (HR 0.86 95% CI 0.79, 0.94; HR 0.83 95% CI 0.75, 0.91 respectively). Our findings suggest that miRNAs impact mRNA translation at multiple levels within the cell cycle.