A scheme of H19 action: New insights of H19 action on Rb-E2F1 signaling and CDK-β-catenin activity. In this proposed model, H19 interacts with macroH2A, and this may consequently lead to de-repression of genes including CDK8, CDK4, and CCND1. Increased CDK4-cyclin D1 complex phosphorylates Rb to disrupt Rb-E2F1 interaction, leading to E2F1 activation. The increase of CDK8 expression enhances the function of mediator complex including MED1, and facilitates the gene regulation by β-catenin. These downstream targets could work in a synergistic way of promoting cell proliferation and increasing cell motility in CRC.
Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264449/cdc27789274PubMedH19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-β-Catenin Signaling in Colorectal Cancer.EBioMedicine2016Ohtsuka MLing HIvan CPichler MMatsushita DGoblirsch MStiegelbauer VShigeyasu KZhang XChen MVidhu FBartholomeusz GAToiyama YKusunoki MDoki YMori MSong SGunther JRKrishnan SSlaby OGoel AAjani JARadovich MCalin GAcolorectal cancerDOID:9256Disease