蛋白磷酸酶2A(protein phosphatases of the type2A,PP2A)是非常重要的蛋白磷酸酶,几乎存在于所有真核细胞中,该酶由3种亚基组成异三聚体结构,包括一个65 k U的结构亚基A(α/β),一个36 k U的催化亚基C(α/β)形成的核心酶和一个多样化...蛋白磷酸酶2A(protein phosphatases of the type2A,PP2A)是非常重要的蛋白磷酸酶,几乎存在于所有真核细胞中,该酶由3种亚基组成异三聚体结构,包括一个65 k U的结构亚基A(α/β),一个36 k U的催化亚基C(α/β)形成的核心酶和一个多样化的调节亚基B[1]。亚基的多样性决定了该酶具有多种催化作用,结合的调节亚基不同,去磷酸化底物就不同,其参与多种细胞信号通路,能调节细胞周期、细胞分化、肿瘤抑制等多种生物学过程[2-3]。展开更多
Background and Aims:Protein phosphatase 2A(PP2A)is associated with many cancers.This study aimed to clarify whether PPP2CA,which encodes the alpha isoform of the catalytic subunit of PP2A,plays a role in hepatocellula...Background and Aims:Protein phosphatase 2A(PP2A)is associated with many cancers.This study aimed to clarify whether PPP2CA,which encodes the alpha isoform of the catalytic subunit of PP2A,plays a role in hepatocellular carcinoma(HCC)and to identify the potential underlying molecular pathways.Methods:Based on bioinformatics,public databases and our in-house RNA-Seq database,we analyzed the clinical value and molecular mechanism of PPP2CA in HCC.Results:Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database,the Gene Expression Omnibus database and our in-house RNA-Seq database.PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues(standardized mean difference:0.69,95%confidence interval[CI]:0.50–0.89).PPP2CA expression was able to differentiate HCC from non-HCC,with an area under the summary receiver operator characteristic curve of 0.79(95%CI:0.75–0.83).Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues.High PPP2CA expression in HCC patients was associated with shorter overall,progression-free and disease-free survival.Potential molecular pathways through which PPP2CA may be involved in HCC were determined using miRWalk 2.0 as well as analysis of Gene Ontology categories,Kyoto Encyclopedia of Genes and Genomes pathways,and protein-protein interaction networks.Conclusions:PPP2CA is up-regulated in HCC and higher expression correlates with worse prognosis.PPP2CA shows potential as a diagnostic marker for HCC.Future studies should examine whether PPP2CA contributes to HCC through the candidate microRNAs,pathways and hub genes identified in this study.展开更多
文摘蛋白磷酸酶2A(protein phosphatases of the type2A,PP2A)是非常重要的蛋白磷酸酶,几乎存在于所有真核细胞中,该酶由3种亚基组成异三聚体结构,包括一个65 k U的结构亚基A(α/β),一个36 k U的催化亚基C(α/β)形成的核心酶和一个多样化的调节亚基B[1]。亚基的多样性决定了该酶具有多种催化作用,结合的调节亚基不同,去磷酸化底物就不同,其参与多种细胞信号通路,能调节细胞周期、细胞分化、肿瘤抑制等多种生物学过程[2-3]。
基金This research was supported by the Innovation and Entrepreneurship Training Program for College Students of Guangxi Medical University(202010598047)the China Postdoctoral Science Foundation(2019M663876XB)+2 种基金the National Natural Science Foundation of China(81960450,82060510)the‘Guangxi BaGui Scholars’Special Fund(2019AQ20)the National Major Special Science and Technology Project(2017ZX10203207).
文摘Background and Aims:Protein phosphatase 2A(PP2A)is associated with many cancers.This study aimed to clarify whether PPP2CA,which encodes the alpha isoform of the catalytic subunit of PP2A,plays a role in hepatocellular carcinoma(HCC)and to identify the potential underlying molecular pathways.Methods:Based on bioinformatics,public databases and our in-house RNA-Seq database,we analyzed the clinical value and molecular mechanism of PPP2CA in HCC.Results:Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database,the Gene Expression Omnibus database and our in-house RNA-Seq database.PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues(standardized mean difference:0.69,95%confidence interval[CI]:0.50–0.89).PPP2CA expression was able to differentiate HCC from non-HCC,with an area under the summary receiver operator characteristic curve of 0.79(95%CI:0.75–0.83).Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues.High PPP2CA expression in HCC patients was associated with shorter overall,progression-free and disease-free survival.Potential molecular pathways through which PPP2CA may be involved in HCC were determined using miRWalk 2.0 as well as analysis of Gene Ontology categories,Kyoto Encyclopedia of Genes and Genomes pathways,and protein-protein interaction networks.Conclusions:PPP2CA is up-regulated in HCC and higher expression correlates with worse prognosis.PPP2CA shows potential as a diagnostic marker for HCC.Future studies should examine whether PPP2CA contributes to HCC through the candidate microRNAs,pathways and hub genes identified in this study.
