The classes Dothideomycetes and Eurotiomycetes include constitutively melanized fungi adapted to extreme conditions and they are widely distributed in diverse hostile habitats worldwide.Yet,despite the growing interes...The classes Dothideomycetes and Eurotiomycetes include constitutively melanized fungi adapted to extreme conditions and they are widely distributed in diverse hostile habitats worldwide.Yet,despite the growing interest in these fungi,there is a considerable gap of knowledge on their functionality.Their genomic analysis is still in its infancy and the possibility to understand their adaptive strategies and exploit their potentialities in bioremediation is very limited.Here,we supply a genome catalog of 118 black fungi,encompassing different ecologies,phylogenies and lifestyles,as a first example of a comparative genomic study at high level of diversity.Results indicate that,as a rule,Dothideomycetes show more variable genome size and that larger genomes are associated with harshest conditions;low temperature tolerance and DNA repair capacity are overrepresented in their genomes.In Eurotiomycetes high temperature tolerance and capacity to metabolize hydrocarbons are more frequently present and these abilities are positively correlated with the human presence.The genomic features are consistent with the prevalent ecologies in the two classes.Indeed,Dothideomycetes are more common in cold and dry environments with high capacity for DNA repair being consistent with the normally highly UV-impacted conditions in their habitats;in contrast,Eurotiomycetes spread mainly in hot human-impacted sites with industrial pollution.Mean annual temperature and isothermality are positively correlated with tolerance to high temperatures in Dothideomycetes,suggesting that,despite their preference for the cold,they are potentially equipped to survive even when temperatures rise due to the global warming.展开更多
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 ...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.展开更多
基金supported by the European Commission under the Marie Sklodowska-Curie Grant Agreement No.702057(DRYLIFE)M.D-B.is supported by a project from the Spanish Ministry of Science and Innovation(PID2020-115813RA-I00)+4 种基金a project of the Fondo Europeo de Desarrollo Regional(FEDER)the Consejería de Transformación Económica,Industria,Conocimiento y Universidades of the Junta de Andalucía(FEDER Andalucía 2014-2020 Objetivo temático'01-Refuerzo de la investigación,el desarrollo tecnológico y la innovación')associated with the research project P20_00879(ANDABIOMA)N.S.receives funding from the ERC(ERC-STG project MetaPG-716575 and ERC-CoG microTOUCH-101045015)J.E.S.is a CIFAR fellow in the Fungal Kingdom:Threats and Opportunities program.T.K.and J.E.S.were partially supported by NIH NIAID R01-GM108492Data analyses performed at the High-Performance Computing Cluster at the University of California Riverside in the Institute of Integrative Genome Biology were supported by NSF grant DBI-1429826 and NIH grant S10-OD016290.
文摘The classes Dothideomycetes and Eurotiomycetes include constitutively melanized fungi adapted to extreme conditions and they are widely distributed in diverse hostile habitats worldwide.Yet,despite the growing interest in these fungi,there is a considerable gap of knowledge on their functionality.Their genomic analysis is still in its infancy and the possibility to understand their adaptive strategies and exploit their potentialities in bioremediation is very limited.Here,we supply a genome catalog of 118 black fungi,encompassing different ecologies,phylogenies and lifestyles,as a first example of a comparative genomic study at high level of diversity.Results indicate that,as a rule,Dothideomycetes show more variable genome size and that larger genomes are associated with harshest conditions;low temperature tolerance and DNA repair capacity are overrepresented in their genomes.In Eurotiomycetes high temperature tolerance and capacity to metabolize hydrocarbons are more frequently present and these abilities are positively correlated with the human presence.The genomic features are consistent with the prevalent ecologies in the two classes.Indeed,Dothideomycetes are more common in cold and dry environments with high capacity for DNA repair being consistent with the normally highly UV-impacted conditions in their habitats;in contrast,Eurotiomycetes spread mainly in hot human-impacted sites with industrial pollution.Mean annual temperature and isothermality are positively correlated with tolerance to high temperatures in Dothideomycetes,suggesting that,despite their preference for the cold,they are potentially equipped to survive even when temperatures rise due to the global warming.
基金funded by a grant from Associazione Italiana per la Ricerca sul Cancro(AIRC)(Grant No.IG19862)to GTpartially funded by the region Friuli Venezia Giulia(D.NAMICA,PORFESR 2007-2013)an intramural grant from the Italian Liver Foundation-ONLUS to CT.
文摘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.
