BACKGROUND B56εis a regulatory subunit of the serine/threonine protein phosphatase 2A,which is abnormally expressed in tumors and regulates various tumor cell functions.At present,the application of B56εin pan-cance...BACKGROUND B56εis a regulatory subunit of the serine/threonine protein phosphatase 2A,which is abnormally expressed in tumors and regulates various tumor cell functions.At present,the application of B56εin pan-cancer lacks a comprehensive analysis,and its role and mechanism in hepatocellular carcinoma(HCC)are still unclear.The Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Profiling Interactive Analysis,and Tumor Immune Estimation Resource databases were used to analyze B56εexpression,prognostic mutations,somatic copy number alterations,and tumor immune characteristics in 33 tumors.The relationships between B56εexpression levels and drug sensitivity,immuno-therapy,immune checkpoints,and human leukocyte antigen(HLA)-related genes were further analyzed.Gene Set Enrichment Analysis(GSEA)was performed to reveal the role of B56εin HCC.The Cell Counting Kit-8,plate cloning,wound healing,and transwell assays were conducted to assess the effects of B56εinterference on the malignant behavior of HCC cells.RESULTS In most tumors,B56εexpression was upregulated,and high B56εexpression was a risk factor for adrenocortical cancer,HCC,pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma(all P<0.05).B56εexpression levels were correlated with a variety of immune cells,such as T helper 17 cells,B cells,and macro-phages.There was a positive correlation between B56εexpression levels with immune checkpoint genes and HLA-related genes(all P<0.05).The expression of B56εwas negatively correlated with the sensitivity of most chemotherapy drugs,but a small number showed a positive correlation(all P<0.05).GSEA analysis showed that B56εexpression was related to the cancer pathway,p53 downstream pathway,and interleukin-mediated signaling in HCC.Knockdown of B56εexpression in HCC cells inhibited the proliferation,migration,and invasion capacity of tumor cells.Core Tip:The expression of protein phosphatase 2A(PP2A)subunit B56εis up-regulated in most tumors,and its high expression is a risk factor for adrenocortical cancer,hepatocellular carcinoma(HCC),pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma.B56εexpression levels correlate with immune cells,immune checkpoint genes,human leukocyte antigen-related genes,and the sensitivity of chemotherapy drugs.In HCC,B56εexpression is related to the cancer pathway.Knockdown of B56εexpression in HCC cells can inhibit the proliferation,migration and invasion capacity of tumor cells.Our study supports PP2A subunit B56εas a prognostic marker and potential therapeutic target for HCC.展开更多
基金National Natural Science Foundation of China,No.82060621,82060607,and 82260664Natural Science Foundation of Guangxi Province,No.2020GXNSFDA297010 and 2020GXNSFAA297142Key Science and Technology Research and Development Program Project of Guangxi,No.AB22035017。
文摘BACKGROUND B56εis a regulatory subunit of the serine/threonine protein phosphatase 2A,which is abnormally expressed in tumors and regulates various tumor cell functions.At present,the application of B56εin pan-cancer lacks a comprehensive analysis,and its role and mechanism in hepatocellular carcinoma(HCC)are still unclear.The Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Profiling Interactive Analysis,and Tumor Immune Estimation Resource databases were used to analyze B56εexpression,prognostic mutations,somatic copy number alterations,and tumor immune characteristics in 33 tumors.The relationships between B56εexpression levels and drug sensitivity,immuno-therapy,immune checkpoints,and human leukocyte antigen(HLA)-related genes were further analyzed.Gene Set Enrichment Analysis(GSEA)was performed to reveal the role of B56εin HCC.The Cell Counting Kit-8,plate cloning,wound healing,and transwell assays were conducted to assess the effects of B56εinterference on the malignant behavior of HCC cells.RESULTS In most tumors,B56εexpression was upregulated,and high B56εexpression was a risk factor for adrenocortical cancer,HCC,pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma(all P<0.05).B56εexpression levels were correlated with a variety of immune cells,such as T helper 17 cells,B cells,and macro-phages.There was a positive correlation between B56εexpression levels with immune checkpoint genes and HLA-related genes(all P<0.05).The expression of B56εwas negatively correlated with the sensitivity of most chemotherapy drugs,but a small number showed a positive correlation(all P<0.05).GSEA analysis showed that B56εexpression was related to the cancer pathway,p53 downstream pathway,and interleukin-mediated signaling in HCC.Knockdown of B56εexpression in HCC cells inhibited the proliferation,migration,and invasion capacity of tumor cells.Core Tip:The expression of protein phosphatase 2A(PP2A)subunit B56εis up-regulated in most tumors,and its high expression is a risk factor for adrenocortical cancer,hepatocellular carcinoma(HCC),pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma.B56εexpression levels correlate with immune cells,immune checkpoint genes,human leukocyte antigen-related genes,and the sensitivity of chemotherapy drugs.In HCC,B56εexpression is related to the cancer pathway.Knockdown of B56εexpression in HCC cells can inhibit the proliferation,migration and invasion capacity of tumor cells.Our study supports PP2A subunit B56εas a prognostic marker and potential therapeutic target for HCC.
