Plant height(PH)is associated with lodging resistance and planting density,which is regulated by a complicated gene network.In this study,we identified a spontaneous dwarfing mutation in maize,m30,with decreased inter...Plant height(PH)is associated with lodging resistance and planting density,which is regulated by a complicated gene network.In this study,we identified a spontaneous dwarfing mutation in maize,m30,with decreased internode number and length but increased internode diameter.A candidate gene,ZmCYP90D1,which encodes a member of the cytochrome P450 family,was isolated by map-based cloning.ZmCYP90D1 was constitutively expressed and showed highest expression in basal internodes,and its protein was targeted to the nucleus.A G-to-A substitution was identified to be the causal mutation,which resulted in a truncated protein in m30.Loss of function of ZmCYP90D1 changed expression of hormoneresponsive genes,in particular brassinosteroid(BR)-responsive genes which is mainly involved in cell cycle regulation and cell wall extension and modification in plants.The concentration of typhasterol(TY),a downstream intermediate of ZmCYP90D1 in the BR pathway,was reduced.A haplotype conferring dwarfing without reducing yield was identified.ZmCYP90D1 was inferred to influence plant height and stalk diameter via hormone-mediated cell division and cell growth via the BR pathway.展开更多
Objective:Tumor-associated macrophages(TAMs)of the M2 phenotype are frequently associated with cancer progression.Invasive cancer cells undergoing epithelial-mesenchymal transition(EMT)have a selective advantage as TA...Objective:Tumor-associated macrophages(TAMs)of the M2 phenotype are frequently associated with cancer progression.Invasive cancer cells undergoing epithelial-mesenchymal transition(EMT)have a selective advantage as TAM activators.Cyclin D1b is a highly oncogenic splice variant of cyclin D1.We previously reported that cyclin D1b enhances the invasiveness of breast cancer cells by inducing EMT.However,the role of cyclin D1b in inducing macrophage differentiation toward tumor-associated macrophage-like cells remains unknown.This study aimed to explore the relationship between breast cancer cells overexpressing cyclin Dlb and TAMs.Methods:Mouse breast cancer 4T1 cells were transfected with cyclin D1b variant and co-cultured with macrophage cells in a Transwell coculture system.The expression of characteristic cytokines in differentiated macrophages was detected using qRT-PCR,ELISA and zymography assay.Tumor-associated macrophage distribution in a transplanted tumor was detected by immunofluorescence staining.The proliferation and migration ability of breast cancer cells was detected using the cell counting kit-8(CCK-8)assay,wound healing assay,Transwell invasion assay,and lung metastasis assay.Expression levels of mRNAs were detected by qRT-PCR.Protein expression levels were detected by Western blotting.The integrated analyses of The Cancer Genome Atlas(TCGA)datasets and bioinformatics methods were adopted to discover gene expression,gene coexpression,and overall survival in patients with breast cancer.Results:After co-culture with breast cancer cells overexpressing cyclin D1b,RAW264.7 macrophages were differentiated into an M2 phenotype.Moreover,differentiated M2-like macrophages promoted the proliferation and migration of breast cancer cells in turn.Notably,these macrophages facilitated the migration of breast cancer cells in vivo.Further investigations indicated that differentiated M2-like macrophages induced EMT of breast cancer cells accompanied with upregulation of TGF-β1 and integrinβ3 expression.Conclusion:Breast cancer cells transfected with cyclin D1b can induce the differentiation of macrophages into a tumor-associated macrophage-like phenotype,which promotes tumor metastasis in vitro and in vivo.展开更多
基金This work was supported by the National Natural Science Foundation of China(U2004144,31971893,32101743)the Key Technologies R&D Program of Henan Province(232102111080)Yunnan Academician Expert Workstation(202305AF150082).
文摘Plant height(PH)is associated with lodging resistance and planting density,which is regulated by a complicated gene network.In this study,we identified a spontaneous dwarfing mutation in maize,m30,with decreased internode number and length but increased internode diameter.A candidate gene,ZmCYP90D1,which encodes a member of the cytochrome P450 family,was isolated by map-based cloning.ZmCYP90D1 was constitutively expressed and showed highest expression in basal internodes,and its protein was targeted to the nucleus.A G-to-A substitution was identified to be the causal mutation,which resulted in a truncated protein in m30.Loss of function of ZmCYP90D1 changed expression of hormoneresponsive genes,in particular brassinosteroid(BR)-responsive genes which is mainly involved in cell cycle regulation and cell wall extension and modification in plants.The concentration of typhasterol(TY),a downstream intermediate of ZmCYP90D1 in the BR pathway,was reduced.A haplotype conferring dwarfing without reducing yield was identified.ZmCYP90D1 was inferred to influence plant height and stalk diameter via hormone-mediated cell division and cell growth via the BR pathway.
基金supported by the National Natural Science Foundation of China(No.81702920,No.82174020).
文摘Objective:Tumor-associated macrophages(TAMs)of the M2 phenotype are frequently associated with cancer progression.Invasive cancer cells undergoing epithelial-mesenchymal transition(EMT)have a selective advantage as TAM activators.Cyclin D1b is a highly oncogenic splice variant of cyclin D1.We previously reported that cyclin D1b enhances the invasiveness of breast cancer cells by inducing EMT.However,the role of cyclin D1b in inducing macrophage differentiation toward tumor-associated macrophage-like cells remains unknown.This study aimed to explore the relationship between breast cancer cells overexpressing cyclin Dlb and TAMs.Methods:Mouse breast cancer 4T1 cells were transfected with cyclin D1b variant and co-cultured with macrophage cells in a Transwell coculture system.The expression of characteristic cytokines in differentiated macrophages was detected using qRT-PCR,ELISA and zymography assay.Tumor-associated macrophage distribution in a transplanted tumor was detected by immunofluorescence staining.The proliferation and migration ability of breast cancer cells was detected using the cell counting kit-8(CCK-8)assay,wound healing assay,Transwell invasion assay,and lung metastasis assay.Expression levels of mRNAs were detected by qRT-PCR.Protein expression levels were detected by Western blotting.The integrated analyses of The Cancer Genome Atlas(TCGA)datasets and bioinformatics methods were adopted to discover gene expression,gene coexpression,and overall survival in patients with breast cancer.Results:After co-culture with breast cancer cells overexpressing cyclin D1b,RAW264.7 macrophages were differentiated into an M2 phenotype.Moreover,differentiated M2-like macrophages promoted the proliferation and migration of breast cancer cells in turn.Notably,these macrophages facilitated the migration of breast cancer cells in vivo.Further investigations indicated that differentiated M2-like macrophages induced EMT of breast cancer cells accompanied with upregulation of TGF-β1 and integrinβ3 expression.Conclusion:Breast cancer cells transfected with cyclin D1b can induce the differentiation of macrophages into a tumor-associated macrophage-like phenotype,which promotes tumor metastasis in vitro and in vivo.
