Clinical Significance of Apurinic/Apyrimidinic Endodeoxyribonuclease 1 and MicroRNA Axis in Hepatocellular Carcinoma  

作　　者：Giovanna Mangiapane Devis Pascut Emiliano Dalla Giulia Antoniali Monica Degrassi Lory Saveria Crocè Veronica De Sanctis Silvano Piazza Giulia Canarutto Claudio Tiribelli Gianluca Tell 

机构地区：[1]Laboratory of Molecular Biology and DNA Repair,Department of Medicine,University of Udine,Udine,Italy [2]Fondazione Italiana Fegato-ONLUS,Liver Cancer Unit,Trieste,Italy [3]Department of Medical Sciences,University of Trieste,Trieste,Italy [4]Clinica Patologie Fegato,Azienda Sanitaria Universitaria Giuliano Isontina(ASUGI),Trieste,Italy [5]NGS Core Facility,Department CIBIO,University of Trento,Trento,Italy [6]Computational Biology,International Centre for Genetic Engineering and Biotechnology,ICGEB,Trieste,Italy

出　　处：《Journal of Clinical and Translational Hepatology》2023年第6期1291-1307,共17页临床与转化肝病杂志（英文版）

基　　金：funded by a grant from Associazione Italiana per la Ricerca sul Cancro(AIRC)(Grant No.IG19862)to GT;partially funded by the region Friuli Venezia Giulia(D.NAMICA,PORFESR 2007-2013);an intramural grant from the Italian Liver Foundation-ONLUS to CT.

摘　　要：Background and Aims:Identification of prognostic factors for hepatocellular carcinoma(HCC)opens new perspectives for therapy.Circulating and cellular onco-miRNAs are noncoding RNAs which can control the expression of genes involved in oncogenesis through post-transcriptional mechanisms.These microRNAs(miRNAs)are considered novel prognostic and predictive factors in HCC.The apurinic/apyrimidinic endodeoxyribonuclease 1(APE1)contributes to the quality control and processing of specific onco-miRNAs and is a negative prognostic factor in several tumors.The present work aims to:a)define APE1 prognostic value in HCC;b)identify miRNAs regulated by APE1 and their relative target genes and c)study their prognostic value.Methods:We used The Cancer Genome Atlas(commonly known as TCGA)data analysis to evaluate the expression of APE1 in HCC.To identify differentially-expressed miRNAs(DEmiRNAs)upon APE1 depletion through specific small interfering RNA,we used NGS and nanostring approaches in the JHH-6 HCC tumor cell line.Bioinformatics analyses were performed to identify signaling pathways involving APE1-regulated miRNAs.Microarray analysis was performed to identify miRNAs correlating with serum APE1 expression.Results:APE1 is considerably overexpressed in HCC tissues compared to normal liver,according to the TCGA-liver HCC(known as LIHC)dataset.Enrichment analyses showed that APE1-regulated miRNAs are implicated in signaling and metabolic pathways linked to cell proliferation,transformation,and angiogenesis,identifying Cyclin Dependent Kinase 6 and Lysosomal Associated Membrane Protein 2 as targets.miR-33a-5p,miR-769,and miR-877 are related to lower overall survival in HCC patients.Through array profiling,we identified eight circulating DE-miRNAs associated with APE1 overexpression.A training phase identified positive association between sAPE1 and miR-3180-3p and miR-769.Conclusions:APE1 regulates specific miRNAs having prognostic value in HCC.

关 键 词：APE1 MIRNAS Prognostic factors Hepatocellular carcinoma 

分 类 号：R735.7[医药卫生—肿瘤]