BACKGROUND As a proteoglycan,VCAN exists in the tumor microenvironment and regulates tumor proliferation,invasion,and metastasis,but its role in hepatocellular carcinoma(HCC)has not yet been elucidated.AIM To investig...BACKGROUND As a proteoglycan,VCAN exists in the tumor microenvironment and regulates tumor proliferation,invasion,and metastasis,but its role in hepatocellular carcinoma(HCC)has not yet been elucidated.AIM To investigate the expression and potential mechanism of action of VCAN in HCC.METHODS Based on The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset,we explored the correlation between VCAN expression and clinical features,and analyzed the prognosis of patients with high and low VCAN expression.The potential mechanism of action of VCAN was explored by Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and gene set enrichment analysis.We also explored immune cell infiltration,immune checkpoint gene expression,and sensitivity of immune checkpoint[programmed cell death protein 1(PD-1)/cytotoxic T lymphocyte antigen 4(CTLA4)]inhibitor therapy in patients with different VCAN expression.VCAN mRNA expression and VCAN methylation in peripheral blood were tested in 100 hepatitis B virus(HBV)-related patients(50 HCC and 50 liver cirrhosis).RESULTS VCAN was highly expressed in HCC tissues,which was associated with a poor prognosis in HCC patients.No significant difference was found in VCAN mRNA expression in blood between patients with HBV-related cirrhosis and those with HCC,but there was a significant difference in VCAN methylation between the two groups.The correlation between VCAN and infiltrations of several different tumor immune cell types(including B cells,CD8+T cells,and eosinophils)was significantly different.VCAN was strongly related to immune checkpoint gene expression and tumor mutation burden,and could be a biomarker of sensitivity to immune checkpoint(PD1/CTLA4)inhibitors.In addition,VCAN mRNA expression was associated with hepatitis B e antigen,HBV DNA,white blood cells,platelets,cholesterol,and coagulation function.CONCLUSION High VCAN level could be a possible biomarker for poor prognosis of HCC,and its immunomodulatory mechanism in HCC warrants investigation.展开更多
[目的]探讨中药山豆根、黄连、穿心莲、姜黄抑制胃癌细胞增殖的共有机制。[方法]用其主成分小檗碱、牛磺酸、穿心莲内酯、姜黄素分别处理胃癌细胞HGC-27后,通过RNA-seq和miRNA-seq鉴定调控胃癌细胞增殖的关键miRNA和其靶基因。[结果]小...[目的]探讨中药山豆根、黄连、穿心莲、姜黄抑制胃癌细胞增殖的共有机制。[方法]用其主成分小檗碱、牛磺酸、穿心莲内酯、姜黄素分别处理胃癌细胞HGC-27后,通过RNA-seq和miRNA-seq鉴定调控胃癌细胞增殖的关键miRNA和其靶基因。[结果]小檗碱、牛磺酸、穿心莲内酯、姜黄素分别处理HGC-27细胞后miR-141-3p表达水平上升。过表达miR-141-3p后能够抑制HGC-27细胞的增殖(2.28±0.10 vs 1.56±0.07,P<0.05)。过表达miR-141-3p后,HGC-27细胞中VCAN的mRNA和蛋白表达水平下降(0.58±0.08 vs 0.13±0.03,P<0.05)。敲低VCAN后HGC-27细胞的增殖水平下降(2.36±0.10 vs 1.60±0.07,P<0.05)。过表达miR-141-3p后,HGC-27细胞中透明质酸与CD44和VCAN的结合均减少。同时,过表达miR-141-3p后CD44和VCAN的相互作用减弱。相比于对照组,过表达CD44能够促进HGC-27细胞增殖(2.27±0.09 vs 3.39±0.09,P<0.05);但是相比于VCAN敲低组,过表达CD44的同时敲低VCAN并没有改变HGC-27细胞的增殖水平。[结论]中药山豆根、黄连、穿心莲、姜黄主要成分处理胃癌细胞后,miR-141-3p/VCAN轴抑制了胃癌细胞的增殖。展开更多
The dermal papilla cells in hair follicles function as critical regulators of hair growth.In particular,alopecia areata(AA)is closely related to the malfunctioning of the human dermal papilla cells(hDPCs).Thus,identif...The dermal papilla cells in hair follicles function as critical regulators of hair growth.In particular,alopecia areata(AA)is closely related to the malfunctioning of the human dermal papilla cells(hDPCs).Thus,identifying the regulatory mechanism of hDPCs is important in inducing hair follicle(HF)regeneration in AA patients.Recently,growing evidence has indicated that 3 untranslated regions(3 UTR)of key genes may participate in the regulatory circuitry underlying cell differentiation and diseases through a socalled competing endogenous mechanism,but none have been reported in HF regeneration.Here,we demonstrate that the 3 UTR of junctional adhesion molecule A(JAM-A)could act as an essential competing endogenous RNA to maintain hDPCs function and promote HF regeneration in AA.We showed that the 3 UTR of JAM-A shares many microRNA(miRNA)response elements,especially miR-221–3p,with versican(VCAN)mRNA,and JAM-A 3 UTR could directly modulate the miRNA-mediated suppression of VCAN in self-renewing hDPCs.Furthermore,upregulated VCAN can in turn promote the expression level of JAM-A.Overall,we propose that JAM-A 3 UTR forms a feedback loop with VCAN and miR-221–3p to regulate hDPC maintenance,proliferation,and differentiation,which may lead to developing new therapies for hair loss.展开更多
We investigated the expression of TIMP1, TIMP2, SPARC, VCAN, and CLEC3B genes, encoded matricellular proteins with pleiotropic functions, and glucose intolerance in obese male subjects with normal and impaired glucose...We investigated the expression of TIMP1, TIMP2, SPARC, VCAN, and CLEC3B genes, encoded matricellular proteins with pleiotropic functions, and glucose intolerance in obese male subjects with normal and impaired glucose tolerance. The purpose of this study was to examine the association between the gene expressions and glucose intolerance in obesity. The results indicate that obesity leads to significant increase of TIMP1, TIMP2, E2F1 and CLEC3B gene expressions in subcutaneous adipose tissue, especially TIMP2 gene. However, more significant increase of the expression of TIMP1 and TIMP2 was found in adipose tissue of obese patients with glucose intolerance. No significant changes were found in the expression of VCAN and SPARC genes in adipose tissue of obese subjects with normal glucose tolerance but increased in the group of obese subjects with glucose intolerance. At the same time, the E2F1 and CLEC3B gene expressions were decreased in adipose tissue of obese patients with glucose intolerance. Results of this study provide evidence that changes in the expression of genes encoded TIMP1, TIMP2, VCAN, SPARC, E2F1 and CLEC3B in subcutaneous adipose tissue of obese individuals associate with glucose intolerance.展开更多
Background:Much still remains unknown about the pathogenesis of brain arteriovenous malformations(AVMs).Previous studies have revealed the abnormal expression of various angiogenesis-related genes in AVMs.To further u...Background:Much still remains unknown about the pathogenesis of brain arteriovenous malformations(AVMs).Previous studies have revealed the abnormal expression of various angiogenesis-related genes in AVMs.To further understand this disease,we sought to identify genes differently expressed in AVMs by means of the gene microarray technique.Methods:Nine AVMs specimen and nine samples of normal vessels are collected.Total RNA isolated from these specimen is hybridized with Oligonucleotide array and gene analysis was conducted.Analyzing data with the help of significance analysis of microarrays(SAM)and a free web-based molecular annotation system 3.0(MAS 3.0).Results:The SAM method identify 37 gene significantly up-regulated and 10 genes down-regulated in AVMs.Conclusions:Among those genes,VACN,SPARK and ARHGAP18 seem to play a facilitating role during the genesis of AVMs.Multiple pathways,as MAPK pathway,may also be involved.展开更多
基金Supported by the National Natural Science Foundation of China,No.31500650 and 81902449the Key Research&Development Program-Social Development of Shaanxi Province,No.2020SF-063Shaanxi Key Research and Development Plans,No.2021SF-227.
文摘BACKGROUND As a proteoglycan,VCAN exists in the tumor microenvironment and regulates tumor proliferation,invasion,and metastasis,but its role in hepatocellular carcinoma(HCC)has not yet been elucidated.AIM To investigate the expression and potential mechanism of action of VCAN in HCC.METHODS Based on The Cancer Genome Atlas Liver Hepatocellular Carcinoma dataset,we explored the correlation between VCAN expression and clinical features,and analyzed the prognosis of patients with high and low VCAN expression.The potential mechanism of action of VCAN was explored by Gene Ontology analysis,Kyoto Encyclopedia of Genes and Genomes analysis,and gene set enrichment analysis.We also explored immune cell infiltration,immune checkpoint gene expression,and sensitivity of immune checkpoint[programmed cell death protein 1(PD-1)/cytotoxic T lymphocyte antigen 4(CTLA4)]inhibitor therapy in patients with different VCAN expression.VCAN mRNA expression and VCAN methylation in peripheral blood were tested in 100 hepatitis B virus(HBV)-related patients(50 HCC and 50 liver cirrhosis).RESULTS VCAN was highly expressed in HCC tissues,which was associated with a poor prognosis in HCC patients.No significant difference was found in VCAN mRNA expression in blood between patients with HBV-related cirrhosis and those with HCC,but there was a significant difference in VCAN methylation between the two groups.The correlation between VCAN and infiltrations of several different tumor immune cell types(including B cells,CD8+T cells,and eosinophils)was significantly different.VCAN was strongly related to immune checkpoint gene expression and tumor mutation burden,and could be a biomarker of sensitivity to immune checkpoint(PD1/CTLA4)inhibitors.In addition,VCAN mRNA expression was associated with hepatitis B e antigen,HBV DNA,white blood cells,platelets,cholesterol,and coagulation function.CONCLUSION High VCAN level could be a possible biomarker for poor prognosis of HCC,and its immunomodulatory mechanism in HCC warrants investigation.
文摘[目的]探讨中药山豆根、黄连、穿心莲、姜黄抑制胃癌细胞增殖的共有机制。[方法]用其主成分小檗碱、牛磺酸、穿心莲内酯、姜黄素分别处理胃癌细胞HGC-27后,通过RNA-seq和miRNA-seq鉴定调控胃癌细胞增殖的关键miRNA和其靶基因。[结果]小檗碱、牛磺酸、穿心莲内酯、姜黄素分别处理HGC-27细胞后miR-141-3p表达水平上升。过表达miR-141-3p后能够抑制HGC-27细胞的增殖(2.28±0.10 vs 1.56±0.07,P<0.05)。过表达miR-141-3p后,HGC-27细胞中VCAN的mRNA和蛋白表达水平下降(0.58±0.08 vs 0.13±0.03,P<0.05)。敲低VCAN后HGC-27细胞的增殖水平下降(2.36±0.10 vs 1.60±0.07,P<0.05)。过表达miR-141-3p后,HGC-27细胞中透明质酸与CD44和VCAN的结合均减少。同时,过表达miR-141-3p后CD44和VCAN的相互作用减弱。相比于对照组,过表达CD44能够促进HGC-27细胞增殖(2.27±0.09 vs 3.39±0.09,P<0.05);但是相比于VCAN敲低组,过表达CD44的同时敲低VCAN并没有改变HGC-27细胞的增殖水平。[结论]中药山豆根、黄连、穿心莲、姜黄主要成分处理胃癌细胞后,miR-141-3p/VCAN轴抑制了胃癌细胞的增殖。
基金supported by the National Natural Science Foundation of China(Grants No.81772075,81772076,and 32071186).
文摘The dermal papilla cells in hair follicles function as critical regulators of hair growth.In particular,alopecia areata(AA)is closely related to the malfunctioning of the human dermal papilla cells(hDPCs).Thus,identifying the regulatory mechanism of hDPCs is important in inducing hair follicle(HF)regeneration in AA patients.Recently,growing evidence has indicated that 3 untranslated regions(3 UTR)of key genes may participate in the regulatory circuitry underlying cell differentiation and diseases through a socalled competing endogenous mechanism,but none have been reported in HF regeneration.Here,we demonstrate that the 3 UTR of junctional adhesion molecule A(JAM-A)could act as an essential competing endogenous RNA to maintain hDPCs function and promote HF regeneration in AA.We showed that the 3 UTR of JAM-A shares many microRNA(miRNA)response elements,especially miR-221–3p,with versican(VCAN)mRNA,and JAM-A 3 UTR could directly modulate the miRNA-mediated suppression of VCAN in self-renewing hDPCs.Furthermore,upregulated VCAN can in turn promote the expression level of JAM-A.Overall,we propose that JAM-A 3 UTR forms a feedback loop with VCAN and miR-221–3p to regulate hDPC maintenance,proliferation,and differentiation,which may lead to developing new therapies for hair loss.
文摘We investigated the expression of TIMP1, TIMP2, SPARC, VCAN, and CLEC3B genes, encoded matricellular proteins with pleiotropic functions, and glucose intolerance in obese male subjects with normal and impaired glucose tolerance. The purpose of this study was to examine the association between the gene expressions and glucose intolerance in obesity. The results indicate that obesity leads to significant increase of TIMP1, TIMP2, E2F1 and CLEC3B gene expressions in subcutaneous adipose tissue, especially TIMP2 gene. However, more significant increase of the expression of TIMP1 and TIMP2 was found in adipose tissue of obese patients with glucose intolerance. No significant changes were found in the expression of VCAN and SPARC genes in adipose tissue of obese subjects with normal glucose tolerance but increased in the group of obese subjects with glucose intolerance. At the same time, the E2F1 and CLEC3B gene expressions were decreased in adipose tissue of obese patients with glucose intolerance. Results of this study provide evidence that changes in the expression of genes encoded TIMP1, TIMP2, VCAN, SPARC, E2F1 and CLEC3B in subcutaneous adipose tissue of obese individuals associate with glucose intolerance.
基金study received financial support from the Beijing Nova program of science and technology.The funding organizations had no role in development of the study or the drafting of the manuscript for publication.
文摘Background:Much still remains unknown about the pathogenesis of brain arteriovenous malformations(AVMs).Previous studies have revealed the abnormal expression of various angiogenesis-related genes in AVMs.To further understand this disease,we sought to identify genes differently expressed in AVMs by means of the gene microarray technique.Methods:Nine AVMs specimen and nine samples of normal vessels are collected.Total RNA isolated from these specimen is hybridized with Oligonucleotide array and gene analysis was conducted.Analyzing data with the help of significance analysis of microarrays(SAM)and a free web-based molecular annotation system 3.0(MAS 3.0).Results:The SAM method identify 37 gene significantly up-regulated and 10 genes down-regulated in AVMs.Conclusions:Among those genes,VACN,SPARK and ARHGAP18 seem to play a facilitating role during the genesis of AVMs.Multiple pathways,as MAPK pathway,may also be involved.
