Dataset Information

MicroRNA Response Elements-Mediated miRNA-miRNA Interactions in Prostate Cancer.

ABSTRACT: The cell is a highly organized system of interacting molecules including proteins, mRNAs, and miRNAs. Analyzing the cell from a systems perspective by integrating different types of data helps revealing the complexity of diseases. Although there is emerging evidence that microRNAs have a functional role in cancer, the role of microRNAs in mediating cancer progression and metastasis remains not fully explored. As the amount of available miRNA and mRNA gene expression data grows, more systematic methods combining gene expression and biological networks become necessary to explore miRNA function. In this work I integrated functional miRNA-target interactions with mRNA and miRNA expression to infer mRNA-mediated miRNA-miRNA interactions. The inferred network represents miRNA modulation through common targets. The network is used to characterize the functional role of microRNA response element (MRE) to mediate interactions between miRNAs targeting the MRE. Results revealed that miRNA-1 is a key player in regulating prostate cancer progression. 11 miRNAs were identified as diagnostic and prognostic biomarkers that act as tumor suppressor miRNAs. This work demonstrates the utility of a network analysis as opposed to differential expression to find important miRNAs that regulate prostate cancer.

SUBMITTER: Alshalalfa M

PROVIDER: S-EPMC3502784 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Publications

MicroRNA Response Elements-Mediated miRNA-miRNA Interactions in Prostate Cancer.

Alshalalfa Mohammed M

Advances in bioinformatics 20121104

The cell is a highly organized system of interacting molecules including proteins, mRNAs, and miRNAs. Analyzing the cell from a systems perspective by integrating different types of data helps revealing the complexity of diseases. Although there is emerging evidence that microRNAs have a functional role in cancer, the role of microRNAs in mediating cancer progression and metastasis remains not fully explored. As the amount of available miRNA and mRNA gene expression data grows, more systematic m ...[more]

PMID: 23193399

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Project description:MicroRNAs are a class of small non-coding regulatory RNA molecules that regulate mRNAs post-transcriptionally. Recent evidence has shown that miRNAs target entire functionally related proteins such as protein complexes and biological pathways. However, characterizing the influence of miRNAs on genes whose encoded proteins are part of protein complexes has not been studied in the context of disease. We propose an entropy-based framework to identify miRNA-mediated dysregulation of functionally related proteins during prostate cancer progression. The proposed framework uses experimentally verified miRNA-target interactions, functionally related proteins and expression data to identify miRNA-influenced protein complexes in prostate cancer, and identify genes that are dysregulated as a result. The framework constructs correlation matrixes between functionally related proteins and miRNAs that have targets in the complex, and assesses the changes in the Shannon entropy of the modules across different stages of prostate cancer. Results reveal that SMAD4 and HDAC containing protein complexes are highly affected and disrupted by miRNAs, particularly miRNA-1 and miRNA-16. Using biological pathways to define functionally related proteins reveals that NF-kB-, RAS-, and Syndecan-mediated pathways are dysregulated due to miRNA-1- and miRNA-16-mediated regulation. These results suggest that miRNA-1 and miRNA-16 are important master regulators of miRNA-mediated regulation in prostate cancer. Moreover, results reveal that miRNAs with high-influence on the disrupted protein complexes are diagnostic and prognostic biomarker candidates for prostate cancer progression. The observation of miRNA-mediated protein complex regulation and miRNA-mediated pathway regulation, with partial experimental verification from previous studies, demonstrates that our framework is a promising approach for the identification of novel miRNAs and protein complexes related to disease progression.

Dataset Information

MicroRNA Response Elements-Mediated miRNA-miRNA Interactions in Prostate Cancer.

Publications

MicroRNA Response Elements-Mediated miRNA-miRNA Interactions in Prostate Cancer.

Similar Datasets

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