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Published on: January 7, 2019
MiRImpact, a new bioinformatic method using complete microRNA expression profiles to assess their overall influence
Alina V Artcibasova1,2, Mikhail B Korzinkin3, Maksim I Sorokin1,3
1a Pathway Pharmaceuticals , Wan Chai , Hong Kong, Hong Kong SAR.
Abstract:
MicroRNAs (miRs) are short noncoding RNA molecules that regulate expression of target mRNAs. Many published sources provide information about miRs and their targets. However, bioinformatic tools elucidating higher level impact of the established total miR profiles, are still largely missing. Recently, we developed a method termed OncoFinder enabling quantification of the activities of intracellular molecular pathways basing on gene expression data. Here we propose a new technique, MiRImpact, which enables to link miR expression data with its estimated outcome on the regulation of molecular pathways, like signaling, metabolic, cytoskeleton rearrangement, and DNA repair pathways. MiRImpact uses OncoFinder rationale for pathway activity calculations, with the major distinctions that (i) it deals with the concentrations of miRs--known regulators of gene products participating in molecular pathways, and (ii) miRs are considered as negative regulators of target molecules, if other is not specified. MiRImpact operates with 2 types of databases: for molecular targets of miRs and for gene products participating in molecular pathways. We applied MiRImpact to compare regulation of human bladder cancer-specific signaling pathways at the levels of mRNA and miR expression. We took 2 most complete alternative databases of experimentally validated miR targets--miRTarBase and DianaTarBase, and an OncoFinder database featuring 2725 gene products and 271 signaling pathways. We showed that the impact of miRs is orthogonal to pathway regulation at the mRNA level, which stresses the importance of studying posttranscriptional regulation of gene expression. We also report characteristic set of miR and mRNA regulation features linked with bladder cancer.
Insights
We introduce MiRImpact, a novel bioinformatic tool linking microRNA (miR) expression to pathway regulation. This method reveals distinct miR and mRNA regulatory features in bladder cancer, highlighting posttranscriptional regulation
Area of Science:
- Bioinformatics
- Molecular Biology
- Cancer Research
Background:
- MicroRNAs (miRs) are crucial regulators of gene expression, impacting various cellular processes.
- Existing bioinformatic tools often lack the capability to analyze the collective impact of miR profiles on molecular pathways.
- Understanding posttranscriptional regulation is vital for deciphering complex biological systems and diseases.
Purpose of the Study:
- To develop and validate MiRImpact, a novel computational technique for assessing microRNA-mediated regulation of molecular pathways.
- To integrate microRNA expression data with gene expression data to infer pathway activities.
- To investigate the interplay between mRNA and microRNA regulation in human bladder cancer.
Main Methods:
- MiRImpact utilizes the OncoFinder framework for pathway activity quantification, adapted for microRNA concentrations.
- The method incorporates databases of experimentally validated microRNA targets (miRTarBase, DianaTarBase) and gene products involved in signaling pathways.
- Application involved comparing mRNA and microRNA expression data in human bladder cancer to analyze pathway regulation.
Main Results:
- MiRImpact successfully links microRNA expression profiles to the regulation of specific molecular pathways.
- The study demonstrates that microRNA impact on pathway regulation is largely orthogonal to mRNA-level regulation.
- Distinctive sets of microRNA and mRNA regulatory features associated with bladder cancer were identified.
Conclusions:
- MiRImpact provides a valuable tool for analyzing the functional consequences of microRNA expression.
- The findings underscore the significance of posttranscriptional regulation by microRNAs in biological pathways.
- The identified regulatory features offer potential insights into the molecular mechanisms of bladder cancer.
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