16 research outputs found
A Densely Interconnected Genome-Wide Network of MicroRNAs and Oncogenic Pathways Revealed Using Gene Expression Signatures
MicroRNAs (miRNAs) are important components of cellular signaling pathways, acting either as pathway regulators or pathway targets. Currently, only a limited number of miRNAs have been functionally linked to specific signaling pathways. Here, we explored if gene expression signatures could be used to represent miRNA activities and integrated with genomic signatures of oncogenic pathway activity to identify connections between miRNAs and oncogenic pathways on a high-throughput, genome-wide scale. Mapping >300 gene expression signatures to >700 primary tumor profiles, we constructed a genome-wide miRNA–pathway network predicting the associations of 276 human miRNAs to 26 oncogenic pathways. The miRNA–pathway network confirmed a host of previously reported miRNA/pathway associations and uncovered several novel associations that were subsequently experimentally validated. Globally, the miRNA–pathway network demonstrates a small-world, but not scale-free, organization characterized by multiple distinct, tightly knit modules each exhibiting a high density of connections. However, unlike genetic or metabolic networks typified by only a few highly connected nodes (“hubs”), most nodes in the miRNA–pathway network are highly connected. Sequence-based computational analysis confirmed that highly-interconnected miRNAs are likely to be regulated by common pathways to target similar sets of downstream genes, suggesting a pervasive and high level of functional redundancy among coexpressed miRNAs. We conclude that gene expression signatures can be used as surrogates of miRNA activity. Our strategy facilitates the task of discovering novel miRNA–pathway connections, since gene expression data for multiple normal and disease conditions are abundantly available
Long-read transcriptome sequencing reveals abundant promoter diversity in distinct molecular subtypes of gastric cancer
10.1186/s13059-021-02261-xGenome Biology2214
Genomic loss of miR-486 regulates tumor progression and the OLFM4 antiapoptotic factor in gastric cancer
10.1158/1078-0432.CCR-10-3152Clinical Cancer Research1792657-2667CCRE
"3G" Trial: An RNA Editing Signature to Guide Gastric Cancer Chemotherapy
10.1158/0008-5472.CAN-20-2872CANCER RESEARCH81102788-279
Regulatory crosstalk between lineage-survival oncogenes KLF5, GATA4 and GATA6 cooperatively promotes gastric cancer development
10.1007/978-1-60327-492-0_23Gut645707-71
Integrative epigenomic and high-throughput functional enhancer profiling reveals determinants of enhancer heterogeneity in gastric cancer
10.1186/s13073-021-00970-3GENOME MEDICINE13
Author Correction: Highly recurrent CBS epimutations in gastric cancer CpG island methylator phenotypes and inflammation (Genome Biology, (2021), 22, 1, (167), 10.1186/s13059-021-02375-2)
10.1186/s13059-021-02405-zGenome Biology22118