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Updated: May 31, 2026
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Identification and functional analysis of epigenetically silenced microRNAs in colorectal cancer cells
Hongli Yan1, Ae-Jin Choi, Byron H Lee
1Genomic Medicine Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States of America.
Abstract:
Abnormal microRNA (miRNA) expression has been linked to the development and progression of several human cancers, and such dysregulation can result from aberrant DNA methylation. While a small number of miRNAs is known to be regulated by DNA methylation, we postulated that such epigenetic regulation is more prevalent. By combining MBD-isolated Genome Sequencing (MiGS) to evaluate genome-wide DNA methylation patterns and microarray analysis to determine miRNA expression levels, we systematically searched for candidate miRNAs regulated by DNA methylation in colorectal cancer cell lines. We found 64 miRNAs to be robustly methylated in HCT116 cells; eighteen of them were located in imprinting regions or already reported to be regulated by DNA methylation. For the remaining 46 miRNAs, expression levels of 18 were consistent with their DNA methylation status. Finally, 8 miRNAs were up-regulated by 5-aza-2'-deoxycytidine treatment and identified to be novel miRNAs regulated by DNA methylation. Moreover, we demonstrated the functional relevance of these epigenetically silenced miRNAs by ectopically expressing select candidates, which resulted in inhibition of growth and migration of cancer cells. In addition to reporting these findings, our study also provides a reliable, systematic strategy to identify DNA methylation-regulated miRNAs by combining DNA methylation profiles and expression data.
Insights
Epigenetic changes, specifically DNA methylation, influence microRNA (miRNA) expression in cancer. This study identifies novel DNA methylation-regulated miRNAs in colorectal cancer, revealing their functional role in inhibiting cancer cell growth and migration.
Area of Science:
- Epigenetics
- Cancer Biology
- Molecular Oncology
Background:
- Abnormal microRNA (miRNA) expression is implicated in cancer development.
- Epigenetic alterations, particularly DNA methylation, are known to cause miRNA dysregulation.
- The full extent of DNA methylation-mediated miRNA regulation in cancer remains largely unexplored.
Purpose of the Study:
- To systematically identify novel microRNAs regulated by DNA methylation in colorectal cancer.
- To investigate the functional significance of these epigenetically regulated miRNAs in cancer progression.
- To establish a robust strategy for discovering DNA methylation-regulated miRNAs.
Main Methods:
- Combined MBD-isolated Genome Sequencing (MiGS) for genome-wide DNA methylation profiling.
- Microarray analysis to assess miRNA expression levels in colorectal cancer cell lines.
- 5-aza-2'-deoxycytidine treatment to validate DNA methylation-regulated miRNAs.
Main Results:
- Identified 64 methylated miRNAs in HCT116 colorectal cancer cells.
- Discovered 8 novel miRNAs epigenetically silenced by DNA methylation.
- Demonstrated that ectopic expression of these miRNAs inhibits cancer cell growth and migration.
Conclusions:
- DNA methylation is a prevalent mechanism regulating miRNA expression in colorectal cancer.
- Novel miRNAs are identified as targets of epigenetic silencing, impacting cancer cell phenotypes.
- The study provides a systematic approach to uncover DNA methylation-driven miRNA dysregulation in cancer.
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