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Dysfunctional miRNA-Mediated Regulation in Chromophobe Renal Cell Carcinoma
Xiaohan Sun1,2, Junying Zhang1
1School of Computer Science and Technology, Xidian University, Xi'an, Shaanxi, P. R. China.
Abstract:
Past research on pathogenesis of a complex disease suggests that differentially expressed message RNAs (mRNAs) can be noted as biomarkers of a disease. However, significant miRNA-mediated regulation change might also be more deep underlying cause of a disease. In this study, a miRNA-mediated regulation module is defined based on GO terms (Gene Ontology terms) from which dysfunctional modules are identified as the suspected cause of a disease. A miRNA-mediated regulation module contains mRNAs annotated to a GO term and MicroRNAs (miRNAs) which regulate the mRNAs. Based on the miRNA-mediated regulation coefficients estimated from the expression profiles of the mRNA and the miRNAs, a SW (single regulation-weight) value is then designed to evaluate the miRNA-mediated regulation change of an mRNA, and the modules with significantly differential SW values are thus identified as dysfunctional modules. The approach is applied to Chromophobe renal cell carcinoma and it identifies 70 dysfunctional miRNA-mediated regulation modules from initial 4381 modules. The identified dysfunctional modules are detected to be comprehensive reflection of chromophobe renal cell carcinoma. The proposed approach suggests that accumulated alteration in miRNA-mediated regulation might cause functional alterations, which further cause a disease. Moreover, this approach can also be used to identify diffentially miRNA-mediated regulated mRNAs showing more comprehensive underlying association with a disease than differentially expressed mRNAs.
Insights
This study introduces a new method to identify disease causes by analyzing microRNA (miRNA)-mediated gene regulation modules. It reveals that altered miRNA regulation, not just gene expression, underlies complex diseases like cancer.
Area of Science:
- Bioinformatics
- Molecular Biology
- Genomics
Background:
- Complex diseases may stem from microRNA (miRNA)-mediated gene regulation, beyond differential gene expression.
- Identifying these regulatory changes is crucial for understanding disease pathogenesis.
Purpose of the Study:
- To define and identify dysfunctional miRNA-mediated regulation modules as potential causes of complex diseases.
- To develop a computational approach for assessing miRNA-mediated regulation changes.
Main Methods:
- Defined miRNA-mediated regulation modules using Gene Ontology (GO) terms and miRNA-mRNA interactions.
- Developed a single regulation-weight (SW) value to quantify miRNA-mediated regulation changes.
- Applied the method to Chromophobe renal cell carcinoma data.
Main Results:
- Identified 70 dysfunctional miRNA-mediated regulation modules from 4381 initial modules in Chromophobe renal cell carcinoma.
- The identified modules comprehensively reflect the disease's characteristics.
- The approach identified differentially miRNA-mediated regulated mRNAs, offering deeper disease associations than differentially expressed mRNAs.
Conclusions:
- Accumulated alterations in miRNA-mediated regulation can lead to functional changes and disease development.
- This method provides a novel framework for uncovering disease mechanisms.
- The approach can identify key mRNAs with significant miRNA-mediated regulation relevant to disease.
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