Abstract:Tumor angiogenesis is a hallmark of liver cancer and is necessary for tumor growth and progression. Supervillin (SVIL) is highly expressed and implicated in several malignant processes of liver cancer. However, the functional relationships between SVIL and tumor angiogenesis in liver cancer have not yet been fully elucidated. The present study was based on bioinformatics analysis, patient tissue sample detection, three-dimensional simulated blood vessel formation, a series of cytological experiments and mouse … Show more
“…5k ). JCAD has been previously implicated in endothelial dysfunction, pathological angiogenesis, and atherosclerotic plaque formation ( 65 ), whereas the role of SVIL in cardiovascular disease remains unknown, but it may promote angiogenesis and epithelial to mesenchymal transition ( 66 ).…”
Ischemic heart disease is the single most common cause of death worldwide with an annual death rate of over 9 million people. Genome-wide association studies have uncovered over 200 genetic loci underlying the disease, providing a deeper understanding of the causal mechanisms leading to it. However, in order to understand ischemic heart disease at the cellular and molecular level, it is necessary to identify the cell-type-specific circuits enabling dissection of driver variants, genes, and signaling pathways in normal and diseased tissues. Here, we provide the first detailed single-cell dissection of the cell types and disease-associated gene expression changes in the living human heart, using cardiac biopsies collected during open-heart surgery from control, ischemic heart disease, and ischemic and non-ischemic heart failure patients. We identify 84 cell types/states, grouped in 12 major cell types. We define markers for each cell type, providing the first extensive reference set for the live human heart. These major cell types include cardiovascular cells (cardiomyocytes, endothelial cells, fibroblasts), rarer cell types (B lymphocytes, neurons, Schwann cells), and rich populations of previously understudied layer-specific epicardial and endocardial cells. In addition, we reveal substantial differences in disease-associated gene expression at the cell subtype level, revealing arterial pericytes as having a central role in the pathogenesis of ischemic heart disease and heart failure. Our results demonstrate the importance of high-resolution cellular subtype mapping in gaining mechanistic insight into human cardiovascular disease.
“…5k ). JCAD has been previously implicated in endothelial dysfunction, pathological angiogenesis, and atherosclerotic plaque formation ( 65 ), whereas the role of SVIL in cardiovascular disease remains unknown, but it may promote angiogenesis and epithelial to mesenchymal transition ( 66 ).…”
Ischemic heart disease is the single most common cause of death worldwide with an annual death rate of over 9 million people. Genome-wide association studies have uncovered over 200 genetic loci underlying the disease, providing a deeper understanding of the causal mechanisms leading to it. However, in order to understand ischemic heart disease at the cellular and molecular level, it is necessary to identify the cell-type-specific circuits enabling dissection of driver variants, genes, and signaling pathways in normal and diseased tissues. Here, we provide the first detailed single-cell dissection of the cell types and disease-associated gene expression changes in the living human heart, using cardiac biopsies collected during open-heart surgery from control, ischemic heart disease, and ischemic and non-ischemic heart failure patients. We identify 84 cell types/states, grouped in 12 major cell types. We define markers for each cell type, providing the first extensive reference set for the live human heart. These major cell types include cardiovascular cells (cardiomyocytes, endothelial cells, fibroblasts), rarer cell types (B lymphocytes, neurons, Schwann cells), and rich populations of previously understudied layer-specific epicardial and endocardial cells. In addition, we reveal substantial differences in disease-associated gene expression at the cell subtype level, revealing arterial pericytes as having a central role in the pathogenesis of ischemic heart disease and heart failure. Our results demonstrate the importance of high-resolution cellular subtype mapping in gaining mechanistic insight into human cardiovascular disease.
“…For example, SVIL can promote cancer cell survival by regulating the level of p53 11 , or in response to signals of intratumoral hypoxia, thereby increasing its own expression, ultimately leading to tumor metastasis and poor survival in liver cancer 10 . In addition, SVIL can promote tumor development in hepatocellular carcinoma by promoting angiogenesis, which can be inhibited by targeting SVIL, and is considered as a potential therapeutic biomarker 12 . However, the expression of SVIL in bladder cancer and its functional relationship with tumors has not yet been reported.…”
SVIL is a member of the villin/gelsolin superfamily and is responsible for encoding supervillin. It has been reported to be closely related to the occurrence and development of various tumors. However, the mechanism of SVIL in bladder cancer has not been reported yet. In this research, we evaluated the relationship between SVIL expression and bladder cancer in public dataset and examined the expression of SVIL in bladder cancer cell lines, tissue microarrays and patients in our cohort. Our work determined that the expression of SVIL in bladder cancer tissue was significantly lower than that in normal tissue. However, in bladder cancer tissues, the high expression of SVIL is significantly associated with poor prognosis. This kind of duality is very novel and has great research value. The expression level of SVIL can well predict the survival time of bladder cancer patients, and is an independent risk factor of bladder cancer patients. The expression of SVIL is also closely related to the immune tumor microenvironment of bladder cancer. Our research provides a basis for personalized therapeutic targets for bladder cancer.
“…JCAD has been previously implicated in endothelial dysfunction, pathological angiogenesis, and atherosclerotic plaque formation, 65 whereas the role of SVIL in cardiovascular disease remains unknown, but it may promote angiogenesis and epithelial to mesenchymal transition. 66 Figure 7 Dissection of JCAD/SVIL locus (A and B) Gene expression module for SVIL in SMCs (A) and pericardial fluid cells (B). GWAS-linked genes in red.…”
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