Guarrera, James V.

Hepatocellular Carcinoma (HCC) is a highly fatal liver cancer with no effective treatments. HCC tumors, formed after long‐term viral or alcohol related inflammation and cirrhosis, have a surprisingly low number of genetic mutations. Prior research has found that epigenetic patterns, such as DNA methylation at gene promoter sites, are common in HCC patients. Recent improvements in genetic sequencing and online genetic databases, have allowed us to identify a set of gene targets, including FMO3, for HCC detection or treatment. The hypothesis is that FMO3 is reduced by epigenetic dysregulation, leading to tumor formation. To find the connection between FMO3, epigenetic events and HCC tumor pathways, our lab created novel HCV‐stable and non‐infected HCC cell lines. We also used Huh7 and Huh7.5 cells to show the epigenetic changes in stressed cells and methylation inhibited cells. To mimic inflammation and stress leading to epigenetic changes, Huh7 cells were exposed to heat shock at 40°C for 40 min. Huh7.5 cells were treated with epigenetic inhibitor 5‐Aza‐2 deoxycytidine. RT‐qPCR and Western Blot show that FMO3 is significantly reduced in stressed cells and upregulated when treated with the methylation inhibitor. These results indicate that FMO3 may be used for early cancer risk detection and/or to improve treatment options by identifying the relationship between epigenetic regulation and tumorigenesis. Support or Funding Information NIH NIDDK 1R01DK110024‐01A1