Knockdown of PAK1IP1 can induce CASP-3-dependent pyroptosis to inhibit the progression of hepatocellular carcinoma

Abstract

AbstractBackgroundHepatocellular carcinoma (HCC), is a prevalent and fatal malignancy originating from hepatic cells with a consistently rising incidence in recent decades. In this study, we aim to identify potential prognostic biomarkers and reveal new mechanism in HCC.MethodsHCC-related datasets (GSE45267 and GSE49515) and TCGA information were downloaded for DEGs, and the common DEGs were WGCNA, protein-protein interaction network (PPI), risk model, expression, survival and prognostic nomogram to determine the key gene related to HCC. Further, the key gene was analyzed by clinical feature analysis, immunoassay and cell experiments to investigate its exact role in HCC.ResultsBased on the above comprehensive analysis, we targeted the key gene PAK1-interacting protein 1(PAK1IP1) with a good prognostic value in HCC. PAK1IP1 was remarkably increased in tumor samples than normal samples, which might be related to immune cell infiltration in liver cancer. It was up-regulated in HCC cells, and its knockdown could suppress HCC proliferation and migration. Besides, ELISA and flow cytometry showed that PAK1IP1 could regulate Lipopolysaccharide (LPS)-induced pyroptosis of HCC cells. Knocking down PAK1IP1 could induce CASP-3-dependent pyroptosis in HCC cells to suppress the development of HCC.ConclusionTo sum up, PAK1IP1 was identified as a promising prognostic biomarker, and knockdown of PAK1IP1 can induce CASP-3-dependent pyroptosis to suppress HCC development, which sheds new light on HCC tumorigenesis.