Anoikis is a specialized form of programmed cell death triggered by the detachment of cells from the extracellular matrix(ECM).Tumor cells that develop resistance to anoikis acquire the ability to detach,migrate,and c...Anoikis is a specialized form of programmed cell death triggered by the detachment of cells from the extracellular matrix(ECM).Tumor cells that develop resistance to anoikis acquire the ability to detach,migrate,and colonize distant sites,ultimately leading to the formation of metastatic tumors.Bit1(Bcl-2 inhibitor of transcription 1),a key effector of anoikis,is released into the cytoplasm upon loss of cell attachment and activates a caspase-independent pathway of apoptosis.Newcastle disease virus(NDV),a pathogen that poses a significant threat to the poultry industry,has also emerged as a promising oncolytic virus capable of selectively targeting and killing tumor cells.However,whether NDV can induce the death of anoikis-resistant tumor cells by activating Bit1 remains unclear.In this study,we utilized physical methods to induce cell suspension as a positive control for anoikis and further examined the expression and cellular localization of Bit1 following NDV infection in tumor cells.The results indicated that both viral infection and cell suspension resulted in partial cell death,accompanied by the translocation of Bit1 from the mitochondria to the cytoplasm and a reduction in its protein levels.Notably,Bit1 expression was found not to significantly affect viral replication.These findings suggest that NDV infection promotes tumor cell death by activating Bit1 translocation,mirroring the effects observed during cell suspension-induced anoikis.In addition,in vivo experiments demonstrated that NDV effectively inhibits the metastasis and growth of melanoma in mice,and that overexpression of Bit1 in tumor cells accelerates this process.This study provides novel insights into NDV-induced tumor cell death and identifies potential targets for understanding the mechanisms of oncolytic virus action.展开更多
Variations in the pathogenicity of Newcastle disease virus(NDV),the agent causing Newcastle disease,are associated with variants of different virulence.A few studies have characterized the expression of microRNAs(miRN...Variations in the pathogenicity of Newcastle disease virus(NDV),the agent causing Newcastle disease,are associated with variants of different virulence.A few studies have characterized the expression of microRNAs(miRNAs)in NDV-infected avian cells.Here,the expression of miRNAs in chicken embryo fibroblasts(CEFs)infected with Herts/33 and LaSota NDV strains(highly virulent and nonvirulent,respectively)was determined using RNA sequencing.miRNAs involved in NDV infection included 562 previously documented and 184 novel miRNAs.miRNA target genes involved transcription factors,cell apoptosis,ubiquitin-mediated proteolysis,and protein processing in the endoplasmic reticulum.Potential target genes associated with autophagy were verified by qRT-PCR.No studies have documented the miRNA profles of CEFs infected with NDVs variants.This study adds to our knowledge of the cellular miRNAs involved in NDV infection and the complex molecular mechanisms mediating virus-host interactions.The results of this study will aid the development of strategies against the chicken virus.展开更多
Herpesviruses account for most of the known virus-encoded miRNAs. Herpesvirus of turkey (HVT), a non-pathogenic avian herpesvirus used as an avian vaccine and viral vector, encodes 28 mature miRNAs. This included HVT-...Herpesviruses account for most of the known virus-encoded miRNAs. Herpesvirus of turkey (HVT), a non-pathogenic avian herpesvirus used as an avian vaccine and viral vector, encodes 28 mature miRNAs. This included HVT-miR-H14-3p that showed almost identical sequence to gga-miR-221, suggesting that it is pirated from the avian host. Although the functional homolog between the two miRNAs has been proposed based on the sequence similarity, the direct experimental evidence is still lacking. In this report, we provide the evidence for the first time that HVT-miR-H14-3p is indeed a gga-miR-221 homolog through modulating the expression of p27Kip1, a known target of miR-221 by binding to its 3’UTR. We also created an HVT-miR-H14-3p deletion virus and show that this miRNA is not essential for in vitro replication.展开更多
基金supported by the National Key Research and Development Program of China(2022YFD1801500)the International Cooperation Project of National Natural Science Foundation of China(32220103012)the Innovation Program of Chinese Academy of Agricultural Sciences(CAAS-CSLPDCP-202402).
文摘Anoikis is a specialized form of programmed cell death triggered by the detachment of cells from the extracellular matrix(ECM).Tumor cells that develop resistance to anoikis acquire the ability to detach,migrate,and colonize distant sites,ultimately leading to the formation of metastatic tumors.Bit1(Bcl-2 inhibitor of transcription 1),a key effector of anoikis,is released into the cytoplasm upon loss of cell attachment and activates a caspase-independent pathway of apoptosis.Newcastle disease virus(NDV),a pathogen that poses a significant threat to the poultry industry,has also emerged as a promising oncolytic virus capable of selectively targeting and killing tumor cells.However,whether NDV can induce the death of anoikis-resistant tumor cells by activating Bit1 remains unclear.In this study,we utilized physical methods to induce cell suspension as a positive control for anoikis and further examined the expression and cellular localization of Bit1 following NDV infection in tumor cells.The results indicated that both viral infection and cell suspension resulted in partial cell death,accompanied by the translocation of Bit1 from the mitochondria to the cytoplasm and a reduction in its protein levels.Notably,Bit1 expression was found not to significantly affect viral replication.These findings suggest that NDV infection promotes tumor cell death by activating Bit1 translocation,mirroring the effects observed during cell suspension-induced anoikis.In addition,in vivo experiments demonstrated that NDV effectively inhibits the metastasis and growth of melanoma in mice,and that overexpression of Bit1 in tumor cells accelerates this process.This study provides novel insights into NDV-induced tumor cell death and identifies potential targets for understanding the mechanisms of oncolytic virus action.
基金This work was financially supported by the National Natural Science Foundation of China(No.31800144 and No.32030108)the Natural Science Foundation of Shanghai(No.18ZR1448700)the Agricultural Science and Technology Innovation Program(ASTIP)of the Chinese Academy of Agricultural Science.
文摘Variations in the pathogenicity of Newcastle disease virus(NDV),the agent causing Newcastle disease,are associated with variants of different virulence.A few studies have characterized the expression of microRNAs(miRNAs)in NDV-infected avian cells.Here,the expression of miRNAs in chicken embryo fibroblasts(CEFs)infected with Herts/33 and LaSota NDV strains(highly virulent and nonvirulent,respectively)was determined using RNA sequencing.miRNAs involved in NDV infection included 562 previously documented and 184 novel miRNAs.miRNA target genes involved transcription factors,cell apoptosis,ubiquitin-mediated proteolysis,and protein processing in the endoplasmic reticulum.Potential target genes associated with autophagy were verified by qRT-PCR.No studies have documented the miRNA profles of CEFs infected with NDVs variants.This study adds to our knowledge of the cellular miRNAs involved in NDV infection and the complex molecular mechanisms mediating virus-host interactions.The results of this study will aid the development of strategies against the chicken virus.
文摘Herpesviruses account for most of the known virus-encoded miRNAs. Herpesvirus of turkey (HVT), a non-pathogenic avian herpesvirus used as an avian vaccine and viral vector, encodes 28 mature miRNAs. This included HVT-miR-H14-3p that showed almost identical sequence to gga-miR-221, suggesting that it is pirated from the avian host. Although the functional homolog between the two miRNAs has been proposed based on the sequence similarity, the direct experimental evidence is still lacking. In this report, we provide the evidence for the first time that HVT-miR-H14-3p is indeed a gga-miR-221 homolog through modulating the expression of p27Kip1, a known target of miR-221 by binding to its 3’UTR. We also created an HVT-miR-H14-3p deletion virus and show that this miRNA is not essential for in vitro replication.
