Abstract：
The cytosolic sulfotransferases (SULTs) are phase II conjugating enzymes, which are widely expressed in the liver and mainly mediate the sulfation of numerous xenobiotics and endogenous compounds. However, the role of various SULTs genes has not been reported in hepatocellular carcinoma (HCC). This study aims to analyze the expression and potential functional roles of SULTs genes in HCC and to identify the role of SULT2A1 in HCC stemness as well as the possible mechanism. We found that all of the 12 SULTs genes were differentially expressed in HCC. Moreover, clinicopathological features and survival rates were also investigated. Multivariate regression analysis showed that SULT2A1 and SULT1C2 could be used as independent prognostic factors in HCC. SULT1C4, SULT1E1, and SULT2A1 were significantly associated with immune infiltration. SULT2A1 deficiency in HCC promoted chemotherapy resistance and stemness maintenance. Mechanistically, silencing of SULT2A1 activated the AKT signaling pathway, on the one hand, promoted the expression of downstream stemness gene c-Myc, on the other hand, facilitated the NRF2 expression to reduce the accumulation of ROS, and jointly increased HCC stemness. Moreover, knockdown NR1I3 was involved in the transcriptional regulation of SULT2A1 in stemness maintenance. In addition, SULT2A1 knockdown HCC cells promoted the proliferation and activation of hepatic stellate cells (HSCs), thereby exerting a potential stroma remodeling effect. Our study revealed the expression and role of SULTs genes in HCC and identified the contribution of SULT2A1 to the initiation and progression of HCC.
摘要：
胞质磺基转移酶（SULTs）是II期缀合酶，它们在肝脏中广泛表达，主要介导许多外源性物质和内源性化合物的硫酸化。然而,各种SULTs基因在肝细胞癌（HCC）中的作用尚未报道。本研究旨在分析SULTs基因在HCC中的表达和潜在的功能作用，并确定SULT2A1在HCC干性中的作用以及可能的机制。我们发现所有12个SULTs基因在HCC中差异表达。此外，还研究了临床病理特征和生存率。多因素回归分析显示SULT2A1和SULT1C2可作为HCC的独立预后因素。SULT1C4、SULT1E1和SULT2A1与免疫浸润显著相干。肝癌中SULT2A1缺乏促进化疗耐药和干性维持。机械上,SULT2A1的沉默激活了AKT信号通路，一方面,促进下游干性基因c-Myc的表达，另一方面,促进NRF2表达以减少ROS的积累，并共同增加HCC的干性。此外，敲低NR1I3参与了精干维持中SULT2A1的转录调控。此外,SULT2A1敲低肝癌细胞促进肝星状细胞（HSC）的增殖和活化，从而发挥潜在的基质重塑作用。我们的研究揭示了SULTs基因在HCC中的表达和作用，并确定了SULT2A1对HCC的发生和发展的贡献。
