WWTR1,a gene related to the TGF-βsignaling pathway,has been elucidated to be involved in oncogenesis in multiple studies.There is,however,no research on its link to immune infiltration in colon cancer.The TCGA databa...WWTR1,a gene related to the TGF-βsignaling pathway,has been elucidated to be involved in oncogenesis in multiple studies.There is,however,no research on its link to immune infiltration in colon cancer.The TCGA database has identified WWTR1,a gene related to the TGF-βsignaling pathway,which is lowly expressed in colon cancer patients compared to normal subjects.Meanwhile,we produced the Kapan-Meier curve with GEO and the TCGA database,which revealed that colon cancer patients with high WWTR1 expression had a poor prognosis.We discovered that high expression of WWTR1 in colon cancer was associated with clinical stage,pathological T-stage,and lymphatic metastasis after examining the clinical characteristics of colon cancer patients.WWTR1 was found to be an independent predictive factor for colon cancer in a multivariate Cox regression study.Infiltration of immunological cells(B cells,CD8^(+)T cells,CD4^(+)T cells,Macrophage,Neutrophil,Dendritic cells)was linked to WWTR1 expression.In colon cancer,WWTR1 expression was also found to be favorably linked with major immune cell markers.According to an analysis of WWTR1 DCGs,GO,and KEGG enrichment analysis,WWTR1 expression levels were associated with ameboidal-type cell migration,focal adhesion,actin binding,Chemical carcinogenesis-reactive oxygen species,Non-alcoholic fatty liver disease,and Alzheimer disease.These findings imply that WWTR1 is a prognostically valuable and important biomarker for colon cancer,and imply that its expression is strongly linked to colon cancer immune infiltration,making it a potential new target for colon cancer biotherapy.展开更多
Chamber maturation is a significant process in cardiac development. Disorders of this crucial process lead to a range of congenital heart defects. Foxc1a is a critical transcription factor reported to regulate the spe...Chamber maturation is a significant process in cardiac development. Disorders of this crucial process lead to a range of congenital heart defects. Foxc1a is a critical transcription factor reported to regulate the specification of cardiac progenitor cells. However, little is known about the role of Foxc1a in modulating chamber maturation. Previously, we reported that foxc1a-null zebrafish embryos exhibit disrupted heart structures and functions. In this study, we observe that ventricle structure and cardiomyocyte proliferation are abolished during chamber maturation in foxc1a-null zebrafish embryos. To observe the endogenous localization of Foxc1a in the hearts of living embryos, we insert eyfp at the foxc1a genomic locus using TALEN. Analysis of the knockin zebrafish show that foxc1a is widely expressed in ventricular cardiomyocytes during chamber development. Cardiac RNA sequencing analysis reveals the downregulated expression of the Hippo signaling effector wwtr1. Dual-luciferase and chromatin immunoprecipitation assays reveal that Foxc1a can bind directly to three sites in the wwtr1 promoter region. Furthermore, wwtr1m RNA overexpression is sufficient to reverse the ventricle defects during chamber maturation. Conditional overexpression of nkx2.5 also partially rescues the ventricular defects during chamber development. These findings demonstrate that wwtr1 and nkx2.5 are direct targets of Foxc1a during ventricular chamber maturation.展开更多
基金supported by the Social Development Projects of Yangzhou(No.YZ2018091)the Major Public Health Projects in Yangzhou+2 种基金Screening Projects of Early Gastrointestinal Diseases(2018)the National Natural Science Foundation of Yangzhou(No.2018YXZX20184,Gastroenterology)Scientific Research Project of Jiangsu Provincial Health Commission(No.M2021039).
文摘WWTR1,a gene related to the TGF-βsignaling pathway,has been elucidated to be involved in oncogenesis in multiple studies.There is,however,no research on its link to immune infiltration in colon cancer.The TCGA database has identified WWTR1,a gene related to the TGF-βsignaling pathway,which is lowly expressed in colon cancer patients compared to normal subjects.Meanwhile,we produced the Kapan-Meier curve with GEO and the TCGA database,which revealed that colon cancer patients with high WWTR1 expression had a poor prognosis.We discovered that high expression of WWTR1 in colon cancer was associated with clinical stage,pathological T-stage,and lymphatic metastasis after examining the clinical characteristics of colon cancer patients.WWTR1 was found to be an independent predictive factor for colon cancer in a multivariate Cox regression study.Infiltration of immunological cells(B cells,CD8^(+)T cells,CD4^(+)T cells,Macrophage,Neutrophil,Dendritic cells)was linked to WWTR1 expression.In colon cancer,WWTR1 expression was also found to be favorably linked with major immune cell markers.According to an analysis of WWTR1 DCGs,GO,and KEGG enrichment analysis,WWTR1 expression levels were associated with ameboidal-type cell migration,focal adhesion,actin binding,Chemical carcinogenesis-reactive oxygen species,Non-alcoholic fatty liver disease,and Alzheimer disease.These findings imply that WWTR1 is a prognostically valuable and important biomarker for colon cancer,and imply that its expression is strongly linked to colon cancer immune infiltration,making it a potential new target for colon cancer biotherapy.
基金supported by the National Natural Science Foundation of China (31970769 and 31671518)。
文摘Chamber maturation is a significant process in cardiac development. Disorders of this crucial process lead to a range of congenital heart defects. Foxc1a is a critical transcription factor reported to regulate the specification of cardiac progenitor cells. However, little is known about the role of Foxc1a in modulating chamber maturation. Previously, we reported that foxc1a-null zebrafish embryos exhibit disrupted heart structures and functions. In this study, we observe that ventricle structure and cardiomyocyte proliferation are abolished during chamber maturation in foxc1a-null zebrafish embryos. To observe the endogenous localization of Foxc1a in the hearts of living embryos, we insert eyfp at the foxc1a genomic locus using TALEN. Analysis of the knockin zebrafish show that foxc1a is widely expressed in ventricular cardiomyocytes during chamber development. Cardiac RNA sequencing analysis reveals the downregulated expression of the Hippo signaling effector wwtr1. Dual-luciferase and chromatin immunoprecipitation assays reveal that Foxc1a can bind directly to three sites in the wwtr1 promoter region. Furthermore, wwtr1m RNA overexpression is sufficient to reverse the ventricle defects during chamber maturation. Conditional overexpression of nkx2.5 also partially rescues the ventricular defects during chamber development. These findings demonstrate that wwtr1 and nkx2.5 are direct targets of Foxc1a during ventricular chamber maturation.
