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 beta-catenin. These downstream targets could work in a synergistic way of promoting cell proliferation and increasing cell motility in colorectal cancer. [Reference](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5264449/) Proteins on this pathway have targeted assays available via the [CPTAC Assay Portal](https://assays.cancer.gov/available_assays?wp_id=WP3969). cdc colorectal cancer DOID:9256 Disease signaling pathway PW:0000003 Pathway Ontology 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