Chen Wei, Wei Tao, Chen Yinghua, Yang Lan, Wu Xiaomin
Department of Oncology, People's Hospital of Huadu District, Guangzhou 510800, People's Republic of China.
Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, People's Republic of China.
Onco Targets Ther. 2020 Dec 14;13:12787-12796. doi: 10.2147/OTT.S260793. eCollection 2020.
Interleukin-1 receptor-associated kinase 1 (IRAK1) was shown to contribute to a variety of cancer-related processes. However, the function of IRAK1 in hepatocellular carcinoma (HCC) pathogenesis has not been investigated in detail.
IRAK1 expression in HCC was examined by immunohistochemistry, qRT-PCR, and Western blot assays. In addition, Huh7 and Hep3B cells were transfected with IRAK1 siRNAs and/or a NOD-like receptor family pyrindomain containing 3 (NLRP3) plasmid. Western blot, EdU staining, and Transwell assays were performed to determine changes of apoptosis, proliferation, migration, and invasion in HCC cells. Moreover, changes in the expression of proteins involved in the MAPKs/NLRP3/IL-1β pathway were confirmed by Western blotting.
IRAK1 was found to be highly upregulated in HCC tissues and cells. Knockdown of IRAK1 signaling prevented the proliferation, invasion, migration, epithelial-mesenchymal transition (EMT) of HCC cells. Mechanistically, we found that activation of the MAPKs/NLRP3/IL-1β pathway could be markedly suppressed by IRAK1 knockdown in HCC cells. Furthermore, our data showed that NLRP3 could partially reverse the reduced aggressive biological behaviors of HCC cells which were caused by RAK1 knockdown.
Knockdown of prevented HCC progression by inhibiting the ability of NLRP3 to block the MAPKs/IL-1β pathway, suggesting that approach as a strategy for treating HCC.
白细胞介素-1受体相关激酶1（IRAK1）已被证明参与多种癌症相关过程。然而，IRAK1在肝细胞癌（HCC）发病机制中的作用尚未得到详细研究。
通过免疫组织化学、qRT-PCR和蛋白质印迹分析检测HCC中IRAK1的表达。此外，用IRAK1小干扰RNA和/或含核苷酸结合寡聚化结构域样受体家族吡咯结构域蛋白3（NLRP3）质粒转染Huh7和Hep3B细胞。进行蛋白质印迹、EdU染色和Transwell分析以确定HCC细胞凋亡、增殖、迁移和侵袭的变化。此外，通过蛋白质印迹证实参与丝裂原活化蛋白激酶/核苷酸结合寡聚化结构域样受体家族吡咯结构域蛋白3/白细胞介素-1β（MAPKs/NLRP3/IL-1β）通路的蛋白质表达变化。
发现IRAK1在HCC组织和细胞中高度上调。敲低IRAK1信号可阻止HCC细胞的增殖、侵袭、迁移和上皮-间质转化（EMT）。机制上，我们发现敲低HCC细胞中的IRAK1可显著抑制MAPKs/NLRP3/IL-1β通路的激活。此外，我们的数据表明NLRP3可部分逆转由RAK1敲低引起的HCC细胞侵袭性生物学行为的降低。
敲低IRAK1通过抑制NLRP3阻断MAPKs/IL-1β通路的能力来阻止HCC进展，提示该方法可作为治疗HCC的一种策略。
