Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
Department of Pathobiology and Immunology, Hebei University of Chinese Medicine, Shijiazhuang 050200, China; School of Basic Medical Sciences, Shanxi University of Chinese Medicine, Jinzhong 030619, China.
Acta Histochem. 2023 May;125(4):152040. doi: 10.1016/j.acthis.2023.152040. Epub 2023 Apr 27.
Yes-associated protein 1 (YAP1) is highly expressed in liver cancer and has been used as an independent prognostic marker for hepatocellular carcinoma (HCC), while inhibition of YAP1 slows down the progression of HCC. Interleukin-18 (IL-18) also tends to be highly expressed in liver cancer. Previous research has proved that dihydroartemisinin (DHA) plays an important role in HCC treatment by reducing YAP1 expression. However, the relationship between YAP1 and IL-18 has not been reported in HCC, especially during DHA therapy.
The purpose of this study was to clarify the relationship between YAP1 and IL-18 in HCC cells, and to explicit the role of IL-18 in the treatment of HCC by DHA.
We found that YAP1 and IL-18 were highly expressed in patients with hepatocellular carcinoma by bioinformatics analysis. Moreover, YAP1 was positively correlated with IL18 in liver cancer. YAP1 and IL18 correlated with immune cell infiltration, notably T cell exhaustion. YAP1 knockdown decreased IL-18 expression, while YAP1 overexpression increased the IL-18 expression in HCC cells. DHA reduced IL-18 expression through YAP1 in HCC cells. Further, DHA reduced the growth of Hepa1-6 cells subcutaneous xenograft tumors by inhibiting the expression of YAP1 and IL-18. However, DHA improved IL-18 in serum and adjacent tissues from DEN/TCPOBOP-induced liver tumor model in C57BL/6 mice.
YAP1 was positively correlated with IL-18 in HCC. DHA reduced the expression of IL-18 by inhibiting YAP1 and plays a role in the treatment of HCC. Our study suggested that IL-18 is a potential target for the treatment of HCC, and DHA is a promising drug for HCC therapy.
The dataset that supports the findings of this study is available from the corresponding author upon reasonable request.
Yes 相关蛋白 1（YAP1）在肝癌中高度表达，已被用作肝细胞癌（HCC）的独立预后标志物，而抑制 YAP1 可减缓 HCC 的进展。白细胞介素-18（IL-18）也倾向于在肝癌中高度表达。先前的研究已经证明二氢青蒿素（DHA）通过降低 YAP1 表达在 HCC 治疗中发挥重要作用。然而，YAP1 与 IL-18 在 HCC 中的关系尚未报道，特别是在 DHA 治疗期间。
本研究旨在阐明 HCC 细胞中 YAP1 与 IL-18 之间的关系，并明确 DHA 治疗 HCC 中 IL-18 的作用。
我们通过生物信息学分析发现 YAP1 和 IL-18 在肝癌患者中高表达。此外，YAP1 在肝癌中与 IL18 呈正相关。YAP1 和 IL18 与免疫细胞浸润相关，特别是 T 细胞耗竭。YAP1 敲低降低了 HCC 细胞中 IL-18 的表达，而 YAP1 过表达增加了 HCC 细胞中 IL-18 的表达。DHA 通过 YAP1 降低了 HCC 细胞中 IL-18 的表达。此外，DHA 通过抑制 YAP1 和 IL-18 的表达，减少 Hepa1-6 细胞皮下异种移植瘤的生长。然而，DHA 改善了 DEN/TCPOBOP 诱导的 C57BL/6 小鼠肝肿瘤模型血清和相邻组织中的 IL-18。
YAP1 在 HCC 中与 IL-18 呈正相关。DHA 通过抑制 YAP1 降低了 IL-18 的表达，在 HCC 治疗中发挥作用。我们的研究表明，IL-18 是 HCC 治疗的潜在靶点，DHA 是 HCC 治疗的一种有前途的药物。
支持本研究结果的数据可应合理要求向通讯作者索取。
