Downregulation of IRAK1 Prevents the Malignant Behavior of Hepatocellular Carcinoma Cells by Blocking Activation of the MAPKs/NLRP3/IL-1β Pathway

Wei Chen,1 Tao Wei,1 Yinghua Chen,2 Lan Yang,3 Xiaomin Wu1 1Department of Oncology, People’s Hospital of Huadu District, Guangzhou 510800, People’s Republic of China; 2Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, People’s Republic of China; 3Department of Laser Beauty, People’s Hospital of Huadu District, Guangzhou 510800, People’s Republic of ChinaCorrespondence: Wei ChenDepartment of Oncology, People’s Hospital of Huadu District, Xinhua Road #48, Huadu District, Guangzhou 510800, People’s Republic of ChinaTel +86 20 86832256Email 13926260691@163.comIntroduction: 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.Methods: 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.Results: 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.Conclusion: Knockdown of IRAK1 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.Keywords: hepatocellular carcinoma, interleukin-1 receptor-associated kinase 1, NOD-like receptor family pyrindomain containing 3, epithelial–mesenchymal transition