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Updated: May 23, 2026
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Identification and functional screening of microRNAs highly deregulated in colorectal cancer
Petra Faltejskova1, Marek Svoboda, Klara Srutova
1Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute (MMCI), Brno, Czech Republic.
Abstract:
MicroRNAs (miRNAs) constitute a robust regulatory network with post-transcriptional regulatory efficiency for almost one half of human coding genes, including oncogenes and tumour suppressors. We determined the expression profile of 667 miRNAs in colorectal cancer (CRC) tissues and paired non-tumoural tissues and identified 42 differentially expressed miRNAs. We chose miR-215, miR-375, miR-378, miR-422a and miR-135b for further validation on an independent cohort of 125 clinically characterized CRC patients and for in vitro analyses. MiR-215, miR-375, miR-378 and miR-422a were significantly decreased, whereas miR-135b was increased in CRC tumour tissues. Levels of miR-215 and miR-422a correlated with clinical stage. MiR-135b was associated with higher pre-operative serum levels of CEA and CA19-9. In vitro analyses showed that ectopic expression of miR-215 decreases viability and migration, increases apoptosis and promotes cell cycle arrest in DLD-1 and HCT-116 colon cancer cell lines. Similarly, overexpression of miR-375 and inhibition of miR-135b led to decreased viability. Finally, restoration of miR-378, miR-422a and miR-375 inhibited G1/S transition. These findings indicate that miR-378, miR-375, miR-422a and miR-215 play an important role in CRC as tumour suppressors, whereas miR-135b functions as an oncogene; both groups of miRNA contribute to CRC pathogenesis.
Insights
Specific microRNAs (miRNAs) show altered expression in colorectal cancer (CRC). Decreased levels of miR-215, miR-375, miR-378, and miR-422a act as tumor suppressors, while increased miR-135b acts as an oncogene in CRC.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression, impacting nearly half of human genes.
- Dysregulation of miRNAs is implicated in various cancers, including colorectal cancer (CRC).
Purpose of the Study:
- To investigate the expression profiles of miRNAs in colorectal cancer (CRC) tissues.
- To identify specific miRNAs that function as tumor suppressors or oncogenes in CRC pathogenesis.
Main Methods:
- Expression profiling of 667 miRNAs in CRC and adjacent non-tumorous tissues.
- Validation of selected miRNAs (miR-215, miR-375, miR-378, miR-422a, miR-135b) in an independent cohort.
- In vitro functional analyses in colon cancer cell lines.
Main Results:
- 42 differentially expressed miRNAs were identified in CRC.
- miR-215, miR-375, miR-378, and miR-422a were significantly decreased in CRC tissues, correlating with clinical stage for miR-215 and miR-422a.
- miR-135b was significantly increased in CRC tissues and associated with elevated tumor markers (CEA, CA19-9).
- In vitro studies demonstrated tumor-suppressive roles for miR-215, miR-375, miR-378, and miR-422a, and an oncogenic role for miR-135b.
Conclusions:
- miR-215, miR-375, miR-378, and miR-422a function as tumor suppressors in colorectal cancer.
- miR-135b acts as an oncogene in colorectal cancer.
- These miRNAs collectively contribute to the pathogenesis of colorectal cancer and may serve as potential therapeutic targets or biomarkers.
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