Erythroleukemia belongs to acute myeloid leukemia(AML)type 6(M6),and treatment remains difficult due to the poor prognosis of the disease.Friend virus(FV)is a complex of two viruses:Friend murine leukemia virus(F-MuLV...Erythroleukemia belongs to acute myeloid leukemia(AML)type 6(M6),and treatment remains difficult due to the poor prognosis of the disease.Friend virus(FV)is a complex of two viruses:Friend murine leukemia virus(F-MuLV)strain along with a defective spleen focus-forming virus(SFFV),which can induce acute eryth-roleukemia in mice.We have previously reported that activation of vagalα7 nicotinic acetylcholine receptor(nAChR)signaling promotes HIV-1 transcription.Whether vagal muscarinic signaling mediates FV-induced erythroleukemia and the underlying mechanisms remain unclear.In this study,sham and vagotomized mice were intraperitoneally injected with FV.FV infection caused anemia in sham mice,and vagotomy reversed this change.FV infection increased erythroblasts ProE,EryA,and EryB cells in the spleen,and these changes were blocked by vagotomy.In bone marrow,FV infection reduced EryC cells in sham mice,an effect that was coun-teracted by vagotomy.FV infection increased choline acetyltransferase(ChAT)expression in splenic CD4^(+)and CD8þT cells,and this change was reversed by vagotomy.Furthermore,the increase of EryA and EryB cells in spleen of FV-infected wild-type mice was reversed after deletion of ChAT in CD4^(+)T cells.In bone marrow,FV infection reduced EryB and EryC cells in sham mice,whereas lack of ChAT in CD4^(+)T cells did not affect this change.Activation of muscarinic acetylcholine receptor 4(mAChR4)by clozapine N-oxide(CNO)significantly increased EryB in the spleen but decreased the EryC cell population in the bone marrow of FV-infected mice.Thus,vagal-mAChR4 signaling in the spleen and bone marrow synergistically promotes the pathogenesis of acute erythroleukemia.We uncover an unrecognized mechanism of neuromodulation in erythroleukemia.展开更多
CARM1(coactivator-associated arginine methyltransferase 1)is a type I protein arginine methyltransferase and a binding protein of the p160 coactivator family.1 Moreover,the research shows that the absence of CARM1 lea...CARM1(coactivator-associated arginine methyltransferase 1)is a type I protein arginine methyltransferase and a binding protein of the p160 coactivator family.1 Moreover,the research shows that the absence of CARM1 leads to impaired adipocyte differentiation?and disrupts normal differentiation of embryonic T cells.3 In addition,other studies have confirmed that CARM1 induces the expression of pluripotent genes Oct4 and Sox2 through methylation modification of histone H3,thereby damaging embryonic stem cell differentiation.4 Furthermore,it can be indicated that CARM1 plays an important role in different types of tumors through various pathways.5 Notably,it is well known that ARAF(v-raf murine sarcoma 3611 viral oncogene homolog)regulates cell proliferation and differentiation abilities.In this study,it is revealed that CARM1 affects the epigenetic modification,transcriptome,and proteome to regulate the expression of related genes in liver cancer,thus regulating cell proliferation,cell metabolism,cell cycle,and other biological processes in liver cancer cells.These results provide a valuable theoretical basis for further exploring the cellular and molecular mechanisms of CARM1 promoting the occurrence and development of liver cancer at the cellular and molecular levels.展开更多
MicroRNAs(miRNAs)have been found to play an important role in human tumorigenesis.A study indicates that the plasma level of miR-933 was elevated in patients with dementia.1 Notably,miR-933(RS79402775)may contribute t...MicroRNAs(miRNAs)have been found to play an important role in human tumorigenesis.A study indicates that the plasma level of miR-933 was elevated in patients with dementia.1 Notably,miR-933(RS79402775)may contribute to the reduction of gastric cancer susceptibility.展开更多
The maternally expressed gene 3(MEG3)acts as an antitumor component in different cancer cells.However,MEG3 variant has been shown to confer cancer susceptibility1 and certain polymorphisms within MEG3 are implicated i...The maternally expressed gene 3(MEG3)acts as an antitumor component in different cancer cells.However,MEG3 variant has been shown to confer cancer susceptibility1 and certain polymorphisms within MEG3 are implicated in cancer risk(rs7158663,rs4081134,and rs11160608).2 Moreover,MEG3-TTCC and MEG3-CCCA promote the differentiation of SCs by activating the JAK2/STAT3 signaling pathway in different degrees.3 In particular,the alleles of MEG3(AA,GA+AA)and MEG3(rs7158663)were associated with an increased risk for human liver cancer.4 Moreover,Sirt2 is a specific NAD-dependent histone deacetylase for H4–K16 and has a strong preference for histone H4K16Ac in their deacetylation activity.5 Nevertheless,the functions and mechanism of MEG3 variant on hepatocarcinogenesis have not yet been well-demonstrated.展开更多
基金from National Natural Science Foundation of China(82241042,81970075,81730001,91942305)National Key Research and Development Program of China(2022YFC2304700)+1 种基金Science and Technology Commission of Shanghai Municipality(20DZ2261200)Innovative research team of high-level local universities in Shanghai(SHSMU-ZDCX20210602).
文摘Erythroleukemia belongs to acute myeloid leukemia(AML)type 6(M6),and treatment remains difficult due to the poor prognosis of the disease.Friend virus(FV)is a complex of two viruses:Friend murine leukemia virus(F-MuLV)strain along with a defective spleen focus-forming virus(SFFV),which can induce acute eryth-roleukemia in mice.We have previously reported that activation of vagalα7 nicotinic acetylcholine receptor(nAChR)signaling promotes HIV-1 transcription.Whether vagal muscarinic signaling mediates FV-induced erythroleukemia and the underlying mechanisms remain unclear.In this study,sham and vagotomized mice were intraperitoneally injected with FV.FV infection caused anemia in sham mice,and vagotomy reversed this change.FV infection increased erythroblasts ProE,EryA,and EryB cells in the spleen,and these changes were blocked by vagotomy.In bone marrow,FV infection reduced EryC cells in sham mice,an effect that was coun-teracted by vagotomy.FV infection increased choline acetyltransferase(ChAT)expression in splenic CD4^(+)and CD8þT cells,and this change was reversed by vagotomy.Furthermore,the increase of EryA and EryB cells in spleen of FV-infected wild-type mice was reversed after deletion of ChAT in CD4^(+)T cells.In bone marrow,FV infection reduced EryB and EryC cells in sham mice,whereas lack of ChAT in CD4^(+)T cells did not affect this change.Activation of muscarinic acetylcholine receptor 4(mAChR4)by clozapine N-oxide(CNO)significantly increased EryB in the spleen but decreased the EryC cell population in the bone marrow of FV-infected mice.Thus,vagal-mAChR4 signaling in the spleen and bone marrow synergistically promotes the pathogenesis of acute erythroleukemia.We uncover an unrecognized mechanism of neuromodulation in erythroleukemia.
基金supported by the National Natural Science Foundation of China(No.82073130).
文摘CARM1(coactivator-associated arginine methyltransferase 1)is a type I protein arginine methyltransferase and a binding protein of the p160 coactivator family.1 Moreover,the research shows that the absence of CARM1 leads to impaired adipocyte differentiation?and disrupts normal differentiation of embryonic T cells.3 In addition,other studies have confirmed that CARM1 induces the expression of pluripotent genes Oct4 and Sox2 through methylation modification of histone H3,thereby damaging embryonic stem cell differentiation.4 Furthermore,it can be indicated that CARM1 plays an important role in different types of tumors through various pathways.5 Notably,it is well known that ARAF(v-raf murine sarcoma 3611 viral oncogene homolog)regulates cell proliferation and differentiation abilities.In this study,it is revealed that CARM1 affects the epigenetic modification,transcriptome,and proteome to regulate the expression of related genes in liver cancer,thus regulating cell proliferation,cell metabolism,cell cycle,and other biological processes in liver cancer cells.These results provide a valuable theoretical basis for further exploring the cellular and molecular mechanisms of CARM1 promoting the occurrence and development of liver cancer at the cellular and molecular levels.
基金supported by grants from the National Natural Science Foundation of China(No.82073130)the Science and Technology Commission of Shanghai Municipality Shanghai Science and Technology Plan Basic Research Field Project(China)(No.20JC1411400).
文摘MicroRNAs(miRNAs)have been found to play an important role in human tumorigenesis.A study indicates that the plasma level of miR-933 was elevated in patients with dementia.1 Notably,miR-933(RS79402775)may contribute to the reduction of gastric cancer susceptibility.
基金supported by the National Natural Science Foundation of China(No.82073130)the Science and Technology Commission of Shanghai Municipality Shanghai Science and Technology Plan Basic Research Field Project(China)(No.19JC1415200)the Science and Technology Commission of Shanghai Municipality Shanghai Science and Technology Plan Basic Research Field Project(China)(No.20JC1411400).
文摘The maternally expressed gene 3(MEG3)acts as an antitumor component in different cancer cells.However,MEG3 variant has been shown to confer cancer susceptibility1 and certain polymorphisms within MEG3 are implicated in cancer risk(rs7158663,rs4081134,and rs11160608).2 Moreover,MEG3-TTCC and MEG3-CCCA promote the differentiation of SCs by activating the JAK2/STAT3 signaling pathway in different degrees.3 In particular,the alleles of MEG3(AA,GA+AA)and MEG3(rs7158663)were associated with an increased risk for human liver cancer.4 Moreover,Sirt2 is a specific NAD-dependent histone deacetylase for H4–K16 and has a strong preference for histone H4K16Ac in their deacetylation activity.5 Nevertheless,the functions and mechanism of MEG3 variant on hepatocarcinogenesis have not yet been well-demonstrated.
