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Published on: March 14, 2019
MicroRNA-21 and PDCD4 expression in colorectal cancer
K H Chang1, N Miller, E A H Kheirelseid
1Department of Surgery, National University of Ireland, Galway, Ireland.
Introduction:
MiRNAs regulate gene expression by binding to target sites and initiating translational repression and/or mRNA degradation. Studies have shown that miR-21 exerts its oncogenic activity by targeting the PDCD4 tumour suppressor 3'-UTR. However, the mechanism of this regulation is poorly understood. In colorectal cancer, loss of PDCD4 has been reported in association with increased tumour aggressiveness and poor prognosis. The purpose of this study was to delineate the interaction between PDCD4 and its oncogenic modulator miR-21 in colorectal cancer.
Methods:
A cohort of 48 colorectal tumours, 61 normal tissues and 7 polyps were profiled for miR-21 and PDCD4 gene expression. A subset of 48 specimens (31 tumours and 17 normal tissues) were analysed for PDCD4 protein expression by immunohistochemistry.
Results:
A significant inverse relationship between miR-21 and PDCD4 gene expression (p < 0.001) was identified by RT-qPCR. In addition, significant reduction of PDCD4 (p < 0.001) expression and reciprocal upregulation of miR-21 (p = 0.005) in a progressive manner from tumour-polyp-normal mucosae was identified. Analysis of protein expression by IHC revealed loss of PDCD4 staining in tumour tissue. Patients with disease recurrence had higher levels of miR-21.
Conclusion:
This study demonstrates the inverse relationship between miR-21 and PDCD4, thus suggesting that miR-21 post-transcriptionally modulates PDCD4 via mRNA degradation. Pharmacological manipulation of the miR-21/PDCD4 axis could represent a novel therapeutic strategy in the treatment of colorectal cancer.
Insights
MicroRNAs (miRNAs) regulate gene expression. In colorectal cancer, miR-21 targets the PDCD4 tumor suppressor, suggesting a novel therapeutic strategy targeting the miR-21/PDCD4 axis.
Area of Science:
- Molecular biology
- Oncology
- Gene regulation
Background:
- MicroRNAs (miRNAs) are key regulators of gene expression, influencing processes like translation repression and mRNA degradation.
- miR-21 is implicated in oncogenesis by targeting the PDCD4 tumor suppressor's 3'-UTR, though its precise mechanism remains unclear.
- Loss of PDCD4 in colorectal cancer correlates with increased tumor aggressiveness and poorer prognosis.
Purpose of the Study:
- To investigate the interaction between PDCD4 and miR-21 in colorectal cancer.
- To elucidate the role of miR-21 in modulating PDCD4 expression within the context of colorectal tumorigenesis.
Main Methods:
- Gene and protein expression analysis of miR-21 and PDCD4 in colorectal tumors, normal tissues, and polyps.
- Quantitative reverse transcription PCR (RT-qPCR) for gene expression profiling.
- Immunohistochemistry (IHC) for assessing PDCD4 protein levels.
Main Results:
- A significant inverse correlation was found between miR-21 and PDCD4 gene expression (p < 0.001).
- PDCD4 expression decreased progressively from normal mucosa to polyps to tumors, while miR-21 expression increased.
- Loss of PDCD4 protein staining was observed in tumor tissues, and higher miR-21 levels were associated with disease recurrence.
Conclusions:
- The study confirms an inverse relationship between miR-21 and PDCD4, indicating miR-21 post-transcriptionally downregulates PDCD4, likely via mRNA degradation.
- Targeting the miR-21/PDCD4 pathway presents a potential novel therapeutic strategy for colorectal cancer treatment.
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