Partial Hepatectomy Promotes the Development of KRASG12V-Induced Hepatocellular Carcinoma in Zebrafish.

Simple Summary: Partial hepatectomy (PH) is a common clinical surgery for managing hepatocellular carcinoma (HCC). A common concern about PH is the high tumor recurrence rate following PH. Previous studies have reported that PH can promote the growth of transplanted HCC in rodents. In the current study, we have used an inducible krasG12V-driven zebrafish HCC model to investigate the effects of PH on the oncogene-induced de novo HCC development. We found that PH can significantly promote the development of krasG12V-induced HCC in zebrafish. This enhancing effect could be attributed to the increased oxidative stress and the enhanced deregulation of molecular factors. Our findings may provide references for the future development of novel therapeutic strategies. The purpose of this study was to investigate the effects of PH on the development of oncogenic krasG12V-induced HCC in zebrafish. The inducible HCC model in Tg(fabp10a:rtTA2s-M2; TRE2:EGFP-krasG12V) zebrafish was used. PH or sham surgery was performed before the induction of oncogenic krasG12V expression in the livers of transgenic zebrafish. Histological analysis was carried out to determine the progression of HCC and other HCC-associated features including hepatocyte proliferation, extracellular matrix production, and local oxidative stress. The similarity between the process of PH-induced liver regeneration and that of krasG12V-induced HCC development was further compared by RNA-Seq analysis. The results show that PH promotes the development of krasG12V-induced HCC in zebrafish possibly through enhancing neutrophil-mediated oxidative stress and promoting the upregulation of s100a1, and the downregulation of ribosome biogenesis. [ABSTRACT FROM AUTHOR]