The purpose of this study was to investigate the effects of PH on the development of oncogenickrasG12V-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 oncogenickrasG12Vexpression 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 ofkrasG12V-induced HCC development was further compared by RNA-Seq analysis. The results show that PH promotes the development ofkrasG12V-induced HCC in zebrafish possibly through enhancing neutrophil-mediated oxidative stress and promoting the upregulation ofs100a1, and the downregulation of ribosome biogenesis.
本研究旨在探讨部分肝切除(PH)对斑马鱼致癌基因krasG12V诱导肝细胞癌(HCC)发展的影响。实验采用Tg(fabp10a:rtTA2s-M2; TRE2:EGFP-krasG12V)转基因斑马鱼的可诱导HCC模型。在转基因斑马鱼肝脏中诱导致癌基因krasG12V表达前,实施PH或假手术。通过组织学分析评估HCC进展及其他HCC相关特征,包括肝细胞增殖、细胞外基质产生和局部氧化应激。进一步通过RNA测序分析比较PH诱导的肝再生过程与krasG12V诱导的HCC发展过程的相似性。结果显示,PH可能通过增强中性粒细胞介导的氧化应激、促进s100a1上调及核糖体生物合成下调,从而促进斑马鱼krasG12V诱导的HCC发展。