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Updated: Feb 11, 2026
Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
miRNA involvement in cell cycle regulation in colorectal cancer cases
Lila E Mullany1, Jennifer S Herrick1, Lori C Sakoda2
1Division of Epidemiology, University of Utah, Salt Lake City, Ut, USA.
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.
Insights
MicroRNAs (miRNAs) regulate cell cycle genes in colorectal cancer. Specific miRNAs, hsa-miR-15a-5p and hsa-miR-20b-5p, are linked to patient survival, suggesting their role in cancer progression.
Area of Science:
- Molecular biology
- Genetics
- Cancer research
Background:
- Uncontrolled cell replication drives carcinogenesis.
- MicroRNAs (miRNAs) are key regulators of genes involved in cell cycle control, DNA repair, and checkpoint pathways.
Purpose of the Study:
- To investigate the interactions between miRNAs and messenger RNAs (mRNAs) within the cell cycle pathway in colorectal cancer.
- To identify specific miRNAs and mRNAs associated with colorectal cancer development and patient survival.
Main Methods:
- Analyzed RNA-Seq data from 217 colorectal cancer patients, comparing tumor and normal tissues.
- Performed differential expression analysis for 123 cell cycle pathway genes and associated miRNAs, adjusting for age and sex.
- Tested associations between differentially expressed miRNAs/mRNAs and colorectal cancer survival, validating miRNA-mRNA interactions via seed region matching.
Main Results:
- Identified 67 dysregulated mRNAs and 48 associated miRNAs.
- Found 102 miRNA-mRNA associations with seed matches, including ten with negative regulatory effects.
- Hsa-miR-15a-5p and hsa-miR-20b-5p were significantly associated with improved colorectal cancer survival (FDR <0.05).
Conclusions:
- MicroRNAs significantly impact mRNA translation within the cell cycle pathway in colorectal cancer.
- Specific miRNAs, hsa-miR-15a-5p and hsa-miR-20b-5p, show potential as prognostic biomarkers for colorectal cancer survival.
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