"Inducing CXCL2 gene expression by targeting H3-Lysine 27 acetylation to reverse liver cancer malignancy"
As research into human genetics grows, the role of epigenetics on molecular phenotype, including cancer, has grown with it. Factors outside of chromosomal DNA, including but not limited to chromatin organization, methylation of DNA, and various histone modifications have been associated with changing transcription levels of genes. Perturbed transcription levels, compared to healthy cells, are associated with various cancers, including liver cancer. CXCL2, chemokine 2 ligand gene, is normally highly expressed in hepatocytes, and is known to play a role in carcinogenesis and cancer metastasis. Its role in cancer progression is related to its function as a nuclear and mitochondrial apoptosis pathway activator, and a cell proliferation pathway inhibitor. In contrast, our research shows HepG2 cells, a liver cancer cell line, do not express CXCL2. To test the role of CXCL2 expression on liver cancer growth rates we attempted to induce transcription of CXCL2 in HepG2 cells. A transfected dCas9-p300 plasmid system was used to place targeted H3K27 acetylation near two promoter regions and one enhancer region of CXCL2. H3K27 acetylation is a specific histone modification found to increase transcription levels of genes near the acetylated histone. The efficacy of both a full length dCas9-p300 plasmid system and a dCas9-p300 core were tested to determine the ability of H3K27 acetylation in inducing targeted expression of CXCL2 and was validated using ChIP-PCR and quantified CXCL2 transcription levels. Growth rates of the transfected cells over the course of 15 days was used to quantify the potential role of CXCL2 expression due to H3K27 acetylation on cellular growth.