Histone Deacetylation is the Primary Epigenetic Mechanism for Silencing of Tumor Suppressor Gene - Tissue Factor Pathway Inhibitor-2 in Hepatocellular Carcinoma Cells
Grade Level at Time of Presentation
Junior
Major
Biology
Institution
University of Louisville
KY House District #
John Yarmouth
KY Senate District #
Mitch McConnell
Faculty Advisor/ Mentor
Shirish Barve
Department
Dept. of Biology
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer related mortality worldwide. With a survival rate of less than 5 percent, a therapeutic treatment is desperately needed to manage this disease. Many epigenetic mechanisms that underlay HCC are being identified. A frequently silenced pathway tissue factor pathway inhibitor-2 (TFPI-2) is a critical tumor suppressor gene. In HCC, inactivation of TFPI-2 leads to tumor growth. Recent research indicated Fas L plays a major role in apoptosis as part of HCC. For the purposes of this study, the phytochemical Curcumin was explored to observe its possible effects on the epigenetic mechanisms underlying HCC. HCC cells underwent curcumin treatment and were examined via real-time polymerase chain reaction (Real-time PCR) chromatin immunoprecipitation (ChIP). Real-time PCR was used to inspect cellular mRNA and protein levels, while ChIP PCR assays were used to check promoter-associated chromatin modifications. As suspected, curcumin effectively reactivated TFPI-2 and upregulated FasL gene expression. Upon further investigation, histone H3 acetylation, which actively correlates with gene transcription, was noticed as well. Overall, curcumin was found to effectively reduce the invasiveness of HCC and cell capability.
Histone Deacetylation is the Primary Epigenetic Mechanism for Silencing of Tumor Suppressor Gene - Tissue Factor Pathway Inhibitor-2 in Hepatocellular Carcinoma Cells
Hepatocellular carcinoma (HCC) is the third leading cause of cancer related mortality worldwide. With a survival rate of less than 5 percent, a therapeutic treatment is desperately needed to manage this disease. Many epigenetic mechanisms that underlay HCC are being identified. A frequently silenced pathway tissue factor pathway inhibitor-2 (TFPI-2) is a critical tumor suppressor gene. In HCC, inactivation of TFPI-2 leads to tumor growth. Recent research indicated Fas L plays a major role in apoptosis as part of HCC. For the purposes of this study, the phytochemical Curcumin was explored to observe its possible effects on the epigenetic mechanisms underlying HCC. HCC cells underwent curcumin treatment and were examined via real-time polymerase chain reaction (Real-time PCR) chromatin immunoprecipitation (ChIP). Real-time PCR was used to inspect cellular mRNA and protein levels, while ChIP PCR assays were used to check promoter-associated chromatin modifications. As suspected, curcumin effectively reactivated TFPI-2 and upregulated FasL gene expression. Upon further investigation, histone H3 acetylation, which actively correlates with gene transcription, was noticed as well. Overall, curcumin was found to effectively reduce the invasiveness of HCC and cell capability.