Background:A kind of tubulin called TUBA1C is implicated in the occurrence and growth of a number of cancers.We mainly investigated the expression,prognostic significance,mechanism and interaction with immune infiltra...Background:A kind of tubulin called TUBA1C is implicated in the occurrence and growth of a number of cancers.We mainly investigated the expression,prognostic significance,mechanism and interaction with immune infiltration of TUBA1C in breast cancer patients.Methods:The expression of TUBA1C as well as its associations with clinical traits and prognosis were examined using the Cancer Genome Atlas,DepMap and Human Protein Atlas databases.The primary pathway involved in breast cancer based on TUBA1C was examined using gene set enrichment analysis software,CancerSEA and the GSCALite database.Then,using ssGSEA and Spearman methods,the interaction between TUBA1C and immune cell infiltration was examined.The R package“pRRophetic”investigated the sensitivity of TUBA1C to chemotherapy and targeted treatment drugs.Results:Patients with BC had significantly higher levels of TUBA1C expression.The poor prognosis of breast cancer patients was linked to the increased expression of TUBA1C.The expression of TUBA1C was identified as an independent risk factor for breast cancer by univariate and multivariate Cox regression analysis.An examination of the gene set enrichment analysis and CanerSEA databases revealed that TUBA1C primarily engages in the cell cycle and DNA replication pathways to have a carcinogenic effect.Th2 cells,aDC,Th1 cells,macrophages,NK CD56dim,neutrophils,DC,Treg,pDC,CD8 T cells,mast cells,NK cells and eosinophils were the 13 types of tumor immune infiltrating cells that TUBA1C was associated with by ssGSEA.Additionally,we discovered that TUBA1C was closely associated with a number of chemotherapy and targeted therapy medications.Our findings suggest that TUBA1C is a novel prognostic predictor of breast cancer,related to immune infiltration and drug sensitivity,and may serve as a new target for breast cancer treatment in the future.Conclusion:According to our study,TUBA1C exerts a carcinogenic effect in breast cancer through oncogenic pathway such as the cell cycle and is associated with immune cell infiltration and predicts response to chemotherapy and targeted therapy.展开更多
The functional specificity of tubulin isotypes has been demonstrated by various neurological diseases caused by an increasing number of mutations in tubulin isotypes.TUBA8 is specifically localized in cerebellar Purki...The functional specificity of tubulin isotypes has been demonstrated by various neurological diseases caused by an increasing number of mutations in tubulin isotypes.TUBA8 is specifically localized in cerebellar Purkinje cells,which exhibitthe most elaborate dendritic trees in the central nervous system.However,the role and related molecular mechanism of TUBA8 in regulating neuronal dendritic morphology remain poorly understood.Here,we report that TUBA8 is required for neuronal dendrite development.As the most divergent member inα-tubulin isotypes,the expression of TUBA8 in Purkinje cells starts at P0,plateaus at P10,and persists into adulthood.Loss of TUBA8 in Purkinje cells induces global dendritic height defects in multiple lobules during development and aging.Meanwhile,TUBA8 deficiency causes age-dependent decreased locomotor activity and anxiety-like behavior.In contrast to TUBA8,TUBA4A,another tubulin isotype highly expressed in Purkinje cells,is not required for dendrite development.Furthermore,the 40th alanine,which differs with any otherα-tubulin isotype and cannot be modified by acetylation,methylation,or lactylation,mediates the promoting effect of TUBA8 in neuronal dendrite development.This study reveals a specific role of TUBA8 in regulating neuronal dendritic morphology and highlights the importance of the 40th amino acid in implementing functions ofα-tubulin isotypes.展开更多
基金supported and funded by the Tai'an Science and Technology Development Plan(Guiding Plan)(No.2018NS0222).
文摘Background:A kind of tubulin called TUBA1C is implicated in the occurrence and growth of a number of cancers.We mainly investigated the expression,prognostic significance,mechanism and interaction with immune infiltration of TUBA1C in breast cancer patients.Methods:The expression of TUBA1C as well as its associations with clinical traits and prognosis were examined using the Cancer Genome Atlas,DepMap and Human Protein Atlas databases.The primary pathway involved in breast cancer based on TUBA1C was examined using gene set enrichment analysis software,CancerSEA and the GSCALite database.Then,using ssGSEA and Spearman methods,the interaction between TUBA1C and immune cell infiltration was examined.The R package“pRRophetic”investigated the sensitivity of TUBA1C to chemotherapy and targeted treatment drugs.Results:Patients with BC had significantly higher levels of TUBA1C expression.The poor prognosis of breast cancer patients was linked to the increased expression of TUBA1C.The expression of TUBA1C was identified as an independent risk factor for breast cancer by univariate and multivariate Cox regression analysis.An examination of the gene set enrichment analysis and CanerSEA databases revealed that TUBA1C primarily engages in the cell cycle and DNA replication pathways to have a carcinogenic effect.Th2 cells,aDC,Th1 cells,macrophages,NK CD56dim,neutrophils,DC,Treg,pDC,CD8 T cells,mast cells,NK cells and eosinophils were the 13 types of tumor immune infiltrating cells that TUBA1C was associated with by ssGSEA.Additionally,we discovered that TUBA1C was closely associated with a number of chemotherapy and targeted therapy medications.Our findings suggest that TUBA1C is a novel prognostic predictor of breast cancer,related to immune infiltration and drug sensitivity,and may serve as a new target for breast cancer treatment in the future.Conclusion:According to our study,TUBA1C exerts a carcinogenic effect in breast cancer through oncogenic pathway such as the cell cycle and is associated with immune cell infiltration and predicts response to chemotherapy and targeted therapy.
基金supported by grants from the National Natural Science Foundation of China(31991194)CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-082).
文摘The functional specificity of tubulin isotypes has been demonstrated by various neurological diseases caused by an increasing number of mutations in tubulin isotypes.TUBA8 is specifically localized in cerebellar Purkinje cells,which exhibitthe most elaborate dendritic trees in the central nervous system.However,the role and related molecular mechanism of TUBA8 in regulating neuronal dendritic morphology remain poorly understood.Here,we report that TUBA8 is required for neuronal dendrite development.As the most divergent member inα-tubulin isotypes,the expression of TUBA8 in Purkinje cells starts at P0,plateaus at P10,and persists into adulthood.Loss of TUBA8 in Purkinje cells induces global dendritic height defects in multiple lobules during development and aging.Meanwhile,TUBA8 deficiency causes age-dependent decreased locomotor activity and anxiety-like behavior.In contrast to TUBA8,TUBA4A,another tubulin isotype highly expressed in Purkinje cells,is not required for dendrite development.Furthermore,the 40th alanine,which differs with any otherα-tubulin isotype and cannot be modified by acetylation,methylation,or lactylation,mediates the promoting effect of TUBA8 in neuronal dendrite development.This study reveals a specific role of TUBA8 in regulating neuronal dendritic morphology and highlights the importance of the 40th amino acid in implementing functions ofα-tubulin isotypes.
