The effect of nutri-epigenomic agent ʺpterostilbeneʺ on the expression of ADAR enzyme(s) in HCC animal model

Abstract

RNA editing is an integral process in generating the diversity of cellular RNA signatures. The best characterized type of RNA editing is A to I (adenosine to inosine) that catalyzed by the ADAR family proteins. HCC is a heterogeneous tumor displaying variable genetic and epigenetic changes. In HCC, aberrant RNA editing may lead to tumor specific transcriptome diversity. Recently, the nutri-epigenomic studies are focusing on the beneficial changes of dietary agent such as pterostilbene on gene expression through epigenetic modifications. However, the effect of pterostilbene on ADAR enzymes expression or RNA editing in HCC has not been investigated. The aim of our work was to investigate the effect of pterostilbene on hepatic gene expression of Adars in DEN-induced rat model of HCC. We assessed the potential effects of pterostilbene at two levels; “co-exposure chemo-prevention” in which pterostilbene was co administered with DEN from the first week of the study and “post-exposure chemo-prevention” in which pterostilbene treatment started after the onset of the key DEN-induced histopathological changes. The current study was conducted at Medical Biochemistry Department, Faculty of Medicine, Ain Shams University from October 2018 to March 2019. Our results revealed that DEN-induced hepatocarcinogenesis indicated by the appearance of prominent hepatic nodules with loss of hepatic architecture and appearance of malignant hepatocytes exhibiting marked pleomorphism, high nucleo-cytoplasmic ratio, prominent nucleoli and frequent mitotic figures. Regarding pterostilbene administration, it attenuates DEN-induced hepatocarcinogenesis; pterostilbene-treated groups exhibited an improvement of the hepatic architecture and minimal atypia of hepatocytes compared to their respective untreated HCC group.