African swine fever(ASF)is an acute,hemorrhagic,and highly contagious disease in pigs caused by the African swine fever virus(ASFV).Our previous studies have demonstrated that deletion of the MGF360-9L gene weakens AS...African swine fever(ASF)is an acute,hemorrhagic,and highly contagious disease in pigs caused by the African swine fever virus(ASFV).Our previous studies have demonstrated that deletion of the MGF360-9L gene weakens ASFV virulence in pigs,yet the underlying mechanism remains unclear.To investigate the mechanism of MGF360-9L regulating ASFV pathogenicity,the relationship between MGF360-9L and host proteins was identified by mass spectrometry.We found that host protein DEAD-box helicase 20(DDX20)interacted with and colocalized with MGF360-9L.Overexpression of DDX20 inhibited ASFV replication,whereas knockdown of DDX20 had the opposite effects.Moreover,DDX20 inhibited ASFV replication by promoting the activation of type I interferon signaling.Surprisingly,DDX20 was gradually degraded following ASFV infection.Mechanistically,MGF360-9L promoted the autophagic degradation of DDX20 by recruiting autophagy-related protein Ras-related protein Rab-1A(Rab1A).Silencing Rab1A suppressed ASFV replication,while overexpression of Rab1A exhibited the opposite effects.Furthermore,Rab1A,MGF360-9L and DDX20 could form a complex to facilitate the degradation of DDX20.Knockdown of Rab1A impaired MGF360-9L-mediated degradation of DDX20 during ASFV infection.In summary,our study demonstrates that MGF360-9L targets DDX20 for autophagy degradation to antagonize its antiviral function and facilitate ASFV replication.This finding broadens our understanding of the regulatory network between ASFV and its host,and provides new insights into the pathogenesis and immune evasion mechanisms of ASFV.展开更多
Objectives:Glioma,as the most lethal primary brain malignancy with poor prognosis,requires further elucidation on the functional role of long noncoding RNA(lncRNA)DDX11 antisense RNA 1(DDX11-AS1)in its pathogenesis,de...Objectives:Glioma,as the most lethal primary brain malignancy with poor prognosis,requires further elucidation on the functional role of long noncoding RNA(lncRNA)DDX11 antisense RNA 1(DDX11-AS1)in its pathogenesis,despite its established oncogenic functions in other cancers.Therefore,this study sought to characterize the oncogenic role and molecular mechanism of DDX11-AS1 in glioma.Methods:DDX11-AS1 expression levels were analyzed in clinical surgical glioma specimens and publicly available datasets.The functional roles of DDX11-AS1 on glioma cell proliferation and migration were investigated using in vitro knockdown and overexpression assays.In vivo tumor growth was assessed using orthotopic glioma-bearing mouse models.To elucidate the regulatory axis involving DDX11-AS1,miR-1183,and E2F transcription factor 7(E2F7),we performed competitive endogenous RNA(ceRNA)analysis and conducted functional rescue experiments via miR-1183 inhibition.Results:DDX11-AS1 expression was markedly upregulated in clinical glioma specimens.Functionally,DDX11-AS1 knockdown significantly suppressed glioma cell proliferation and migration in vitro,while its overexpression exacerbated these malignant phenotypes.Orthotopic glioma-bearingmouse models confirmed that DDX11-AS1 drives in vivo glioma tumor growth.Mechanistically,DDX11-AS1 functions as a ceRNA by competitively interacting with miR-1183.Critically,inhibition of miR-1183 rescued the suppressive effects of DDX11-AS1 knockdown on glioma tumorigenic phenotypes and restored E2F7 expression levels.Conclusions:This study demonstrates that lncRNA DDX11-AS1 promotes glioma progression by regulating the miR-1183/E2F7 axis,indicating a potential therapeutic target for glioma.展开更多
基金supported by the grants from the open competition program of top ten critical priorities of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province(2024KJ14)the Fundamental Research Funds for the Central Universities(lzujbky-2022-ct02)+7 种基金the Project of National Center of Technology Innovation for Pigs(NCTIP-XD/C03)the Youth Innovation Program of the Chinese Academy of Agricultural Sciences(Y2025QC33)the Major Science and Technology Project of Gansu Province(22ZD6NA001 and 22ZD6NA012)the Innovation Program of Chinese Academy of Agricultural Sciences(CAAS-CSLPDCP-2023002 and CAAS-ASTIP-2025-LVRI)the China Postdoctoral Science Foundation(2023M743830)the Earmarked Fund for CARS-35 and CARS-39-13he Fundamental Research Funds for Innovation Team of Gansu Province(23JRRA546,23JRRA548)the Basic Scientific Research Fund of LVRI(1610312021009).
文摘African swine fever(ASF)is an acute,hemorrhagic,and highly contagious disease in pigs caused by the African swine fever virus(ASFV).Our previous studies have demonstrated that deletion of the MGF360-9L gene weakens ASFV virulence in pigs,yet the underlying mechanism remains unclear.To investigate the mechanism of MGF360-9L regulating ASFV pathogenicity,the relationship between MGF360-9L and host proteins was identified by mass spectrometry.We found that host protein DEAD-box helicase 20(DDX20)interacted with and colocalized with MGF360-9L.Overexpression of DDX20 inhibited ASFV replication,whereas knockdown of DDX20 had the opposite effects.Moreover,DDX20 inhibited ASFV replication by promoting the activation of type I interferon signaling.Surprisingly,DDX20 was gradually degraded following ASFV infection.Mechanistically,MGF360-9L promoted the autophagic degradation of DDX20 by recruiting autophagy-related protein Ras-related protein Rab-1A(Rab1A).Silencing Rab1A suppressed ASFV replication,while overexpression of Rab1A exhibited the opposite effects.Furthermore,Rab1A,MGF360-9L and DDX20 could form a complex to facilitate the degradation of DDX20.Knockdown of Rab1A impaired MGF360-9L-mediated degradation of DDX20 during ASFV infection.In summary,our study demonstrates that MGF360-9L targets DDX20 for autophagy degradation to antagonize its antiviral function and facilitate ASFV replication.This finding broadens our understanding of the regulatory network between ASFV and its host,and provides new insights into the pathogenesis and immune evasion mechanisms of ASFV.
基金supported by Shenzhen Science and Technology Program(JCYJ20220530152614033,JCYJ20230807142213027)Funding Statement Special Fund for Economic and Technological Development in Longgang District,Shenzhen(LGKCYLWS2023028).
文摘Objectives:Glioma,as the most lethal primary brain malignancy with poor prognosis,requires further elucidation on the functional role of long noncoding RNA(lncRNA)DDX11 antisense RNA 1(DDX11-AS1)in its pathogenesis,despite its established oncogenic functions in other cancers.Therefore,this study sought to characterize the oncogenic role and molecular mechanism of DDX11-AS1 in glioma.Methods:DDX11-AS1 expression levels were analyzed in clinical surgical glioma specimens and publicly available datasets.The functional roles of DDX11-AS1 on glioma cell proliferation and migration were investigated using in vitro knockdown and overexpression assays.In vivo tumor growth was assessed using orthotopic glioma-bearing mouse models.To elucidate the regulatory axis involving DDX11-AS1,miR-1183,and E2F transcription factor 7(E2F7),we performed competitive endogenous RNA(ceRNA)analysis and conducted functional rescue experiments via miR-1183 inhibition.Results:DDX11-AS1 expression was markedly upregulated in clinical glioma specimens.Functionally,DDX11-AS1 knockdown significantly suppressed glioma cell proliferation and migration in vitro,while its overexpression exacerbated these malignant phenotypes.Orthotopic glioma-bearingmouse models confirmed that DDX11-AS1 drives in vivo glioma tumor growth.Mechanistically,DDX11-AS1 functions as a ceRNA by competitively interacting with miR-1183.Critically,inhibition of miR-1183 rescued the suppressive effects of DDX11-AS1 knockdown on glioma tumorigenic phenotypes and restored E2F7 expression levels.Conclusions:This study demonstrates that lncRNA DDX11-AS1 promotes glioma progression by regulating the miR-1183/E2F7 axis,indicating a potential therapeutic target for glioma.
