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/ Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP3969 CPTAC Assay Portal] cdc colorectal cancer DOID:9256 Disease 27789274 PubMed H19 Noncoding RNA, an Independent Prognostic Factor, Regulates Essential Rb-E2F and CDK8-β-Catenin Signaling in Colorectal Cancer. EBioMedicine 2016 Ohtsuka M Ling H Ivan C Pichler M Matsushita D Goblirsch M Stiegelbauer V Shigeyasu K Zhang X Chen M Vidhu F Bartholomeusz GA Toiyama Y Kusunoki M Doki Y Mori M Song S Gunther JR Krishnan S Slaby O Goel A Ajani JA Radovich M Calin GA signaling pathway PW:0000003 Pathway Ontology