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Published on: March 30, 2019
MiRNA target enrichment analysis of co-expression network modules reveals important miRNAs and their roles in breast
Mohammad Javad Bazyari1, Seyed Hamid Aghaee-Bakhtiari2,1
1Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, 37552 Mashhad University of Medical Sciences , Mashhad, Iran.
Abstract:
Breast cancer has the highest incidence and is the fifth cause of death in cancers. Progression is one of the important features of breast cancer which makes it a life-threatening cancer. MicroRNAs are small RNA molecules that have pivotal roles in the regulation of gene expression and they control different properties in breast cancer such as progression. Recently, systems biology offers novel approaches to study complicated biological systems like miRNAs to find their regulatory roles. One of these approaches is analysis of weighted co-expression network in which genes with similar expression patterns are considered as a single module. Because the genes in one module have similar expression, it is rational to think the same regulatory elements such as miRNAs control their expression. Herein, we use WGCNA to find important modules related to breast cancer progression and use hypergeometric test to perform miRNA target enrichment analysis and find important miRNAs. Also, we use negative correlation between miRNA expression and modules as the second filter to ensure choosing the right candidate miRNAs regarding to important modules. We found hsa-mir-23b, hsa-let-7b and hsa-mir-30a are important miRNAs in breast cancer and also investigated their roles in breast cancer progression.
Insights
This study identifies key microRNAs (miRNAs) involved in breast cancer progression using systems biology approaches. Researchers found hsa-mir-23b, hsa-let-7b, and hsa-mir-30a play crucial roles in this life-threatening cancer.
Area of Science:
- Oncology
- Genomics
- Systems Biology
Background:
- Breast cancer is a leading cause of cancer incidence and mortality.
- Cancer progression is a critical factor in breast cancer's lethality.
- MicroRNAs (miRNAs) are key regulators of gene expression influencing cancer properties, including progression.
Purpose of the Study:
- To identify significant modules associated with breast cancer progression using weighted gene co-expression network analysis (WGCNA).
- To discover critical miRNAs regulating breast cancer progression through target enrichment analysis.
- To validate candidate miRNAs by examining their negative correlation with identified gene modules.
Main Methods:
- Weighted Gene Co-expression Network Analysis (WGCNA) to identify gene modules related to breast cancer progression.
- Hypergeometric test for miRNA target enrichment analysis.
- Correlation analysis to link miRNA expression with module activity.
Main Results:
- Identification of key gene modules significantly associated with breast cancer progression.
- Discovery of specific miRNAs, including hsa-mir-23b, hsa-let-7b, and hsa-mir-30a, as important regulators.
- Validation of these miRNAs through negative correlation with relevant gene modules.
Conclusions:
- hsa-mir-23b, hsa-let-7b, and hsa-mir-30a are identified as significant miRNAs in breast cancer progression.
- Systems biology approaches, particularly WGCNA, are effective for uncovering miRNA regulatory roles in cancer.
- Further investigation into the roles of these miRNAs may offer new therapeutic strategies for breast cancer.
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