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Genome-wide perturbations by miRNA map onto functional cancer pathways identifying regulators of chromatin modifiers

ABSTRACT: Genome-wide perturbations by miRNA map onto functional cancer pathways identifying regulators of chromatin modifiers

ORGANISM(S): Homo sapiens

PROVIDER: GSE64020 | GEO | 2015/03/31

SECONDARY ACCESSION(S): PRJNA269767

REPOSITORIES: GEO

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Genome-wide perturbations by miRNA map onto functional cancer pathways identifying regulators of chromatin modifiers

Project description:Genome-wide perturbations by miRNA map onto functional cancer pathways identifying regulators of chromatin modifiers Total RNA obtained from cancer cell lines transfected with miR-365-3p for 24 hours compared to controls.

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Genome-wide perturbations by miRNAs map onto functional cellular pathways, identifying regulators of chromatin modifiers.

Project description:BackgroundRegulation of gene expression by microRNAs (miRNAs) is critical for determining cellular fate and function. Dysregulation of miRNA expression contributes to the development and progression of multiple diseases. miRNA can target multiple mRNAs, making deconvolution of the effects of miRNA challenging and the complexity of regulation of cellular pathways by miRNAs at the functional protein level remains to be elucidated. Therefore, we sought to determine the effects of expression of miRNAs in breast and ovarian cancer cells on cellular pathways by measuring systems-wide miRNA perturbations to protein and phosphoproteins.MethodsWe measure protein level changes by reverse-phase protein array (RPPA) in MDA-MB-231, SKOV3.ip1 and HEYA8 cancer cell lines transfected by a library of 879 human miRNA mimics.ResultsThe effects of multiple miRNAs-protein networks converged in five broad functional clusters of miRNA, suggesting a broad overlap of miRNA action on cellular pathways. Detailed analysis of miRNA clusters revealed novel miRNA/cell cycle protein networks, which we functionally validated. De novo phosphoprotein network estimation using Gaussian graphical modeling, using no priors, revealed known and novel protein interplay, which we also observed in patient ovarian tumor proteomic data. We identified several miRNAs that have pluripotent activities across multiple cellular pathways. In particular we studied miR-365a whose expression is associated with poor survival across several cancer types and demonstrated that anti-miR-365 significantly reduced tumor formation in animal models.ConclusionsMapping of miRNA-induced protein and phosphoprotein changes onto pathways revealed new miRNA-cellular pathway connectivity, paving the way for targeting of dysregulated pathways with potential miRNA-based therapeutics.

| S-EPMC5516802 | biostudies-literature

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Project description:Revealing Dominant Regulatory MicroRNA-495-3p that Governs Multiple Epigenetic Modifiers in Gastric Carcinogenesis In this study, we identified miR-495-3p targeting multiple epigenetic modifiers through comprehensive miRNA and mRNA profiling analysis with in silico target prediction in GC. Western blotting assay or quantitative real time PCR was performed to confirm the expression of miR-495-3p and targets of it. We applied miRNA mimics to ectopic overexpression in gastric cancer cells and observed tumor suppressive effects of miR-495-3p in the growth and metastasis of cancer. Also, we confirmed the status of CpG islands of miR-495-3p promoter using methylation specific PCR analysis.

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