SUMO化修饰是一种把小泛素相关修饰物(small ubiquition related modifier,SUMO)共价连接到细胞内靶蛋白半胱氨酸残基上的一种蛋白质翻译后修饰。SUMO化修饰参与并调控着多种细胞进程,如转录调控、核转运和信号转导等。SUMO化修饰是一...SUMO化修饰是一种把小泛素相关修饰物(small ubiquition related modifier,SUMO)共价连接到细胞内靶蛋白半胱氨酸残基上的一种蛋白质翻译后修饰。SUMO化修饰参与并调控着多种细胞进程,如转录调控、核转运和信号转导等。SUMO化修饰是一种动态可逆的修饰方式。SUMO特异性蛋白酶(SUMO-specific proteases,SENPs)可以使SUMO化修饰的蛋白质发生去SUMO化,在维持细胞内SUMO化与去SUMO化的平衡中起重要作用。研究表明,SENPs与多种癌症的发生发展密切相关,如SENP1能直接调节多条致癌通路,诱发正常的前列腺上皮细胞状态异常。癌细胞中的SENP3能诱导血管生成。因此,对去SUMO化机制研究可以为开发癌症治疗药物提供新的思路。展开更多
Microbial selenite(Se(Ⅳ)) reduction to elemental selenium nanoparticles(SeNPs) and chromate(Cr(Ⅵ)) remediation constitute effective detoxification processes. The strain Bacillus wiedmannii ES2-45 can efficiently red...Microbial selenite(Se(Ⅳ)) reduction to elemental selenium nanoparticles(SeNPs) and chromate(Cr(Ⅵ)) remediation constitute effective detoxification processes. The strain Bacillus wiedmannii ES2-45 can efficiently reduce 5 mmol/L Se(Ⅳ) into SeNPs over 14 h and 1 mmol/L Cr(Ⅵ) within 36 h. Proteomic analysis and qRT-PCR revealed that reductases, including dithiol oxidoreductase(DsbA), Fe-S biosynthesis domain-containing protein(Fes),and aldose-6-phosphate reductase(Aldo), and bacillithiol(BSH) were involved in Se(Ⅳ) reduction. Heterologous expression further confirmed the Se(Ⅳ)-reducing function of three genes and enhanced the Se(Ⅳ) and Cr(Ⅵ) resistance ability. Moreover, the difference between Se(Ⅳ) treatments and controls both intra-and extra-cellular BSH concentration per biomass indicated that BSH contributes to Se(Ⅳ) reduction. Selenium-fortified rice was obtained by foliar spray of SeNPs synthesized by the strain ES2-45. To the best of our knowledge, DsbA and Aldo reductase were firstly verified for the role in Se(Ⅳ) reduction and Cr(Ⅵ)resistance. Importantly, it is a promising strategy that B. wiedmannii ES2-45 is served as an efficient bacterium for SeNP synthesis, selenium biofortification and heavy metal bioremediation.展开更多
Background:Small ubiquitin-like modifier(SUMO)-specific proteases(SENPs)cleave the isopeptidic bond between SUMO1/2/3 and protein substrates,thus regulating the structure,activity,and lifetime of a variety of proteins...Background:Small ubiquitin-like modifier(SUMO)-specific proteases(SENPs)cleave the isopeptidic bond between SUMO1/2/3 and protein substrates,thus regulating the structure,activity,and lifetime of a variety of proteins.Recently,accumulating evidence has suggested that SENPs play a role in the initiation and progression of human cancers.Nevertheless,the potential role of the SENP family of proteins in liver cancer has yet to be fully elucidated.Methods:This study conducted a comprehensive bioinformatics analysis of the SENP family in liver cancer,including differential expression profiling,survival analysis,mutation and copy number variations(CNVs)assessment,immune infiltration and drug sensitivity correlation,functional enrichment analyses using data from The Cancer Genome Atlas(TCGA),Clinical Proteomic Tumor Analysis Consortium(CPTAC),LinkedOmics,and other public databases.Furthermore,we performed in vitro experiments using Huh-7 and Hep-3B cell lines to investigate the functional roles of SENP1 and SENP3 in hepatocellular carcinoma cell proliferation,colony formation,and migration.Results:Our results indicated that SENP1,3,and 7 were significantly overexpressed in liver hepatocellular carcinoma(LIHC).Elevated expressions of SENP1,3,and 7 are positively correlated with poor overall survival(OS)in LIHC patients.In addition,SENP1,3,and 7 expressions are related to immune infiltration and drug sensitivity.SENP1,3,and 7 co-expressed genes were enriched in mitochondrial function,ribosomal translation,and cell cycle control.Conclusion:SENP1,3,and 7 are prognostic biomarkers and potential therapeutic targets for LIHC.Knockdown of SENP1 and SENP3 inhibited the proliferation,clonogenicity,and migration of hepatocellular carcinoma cells.展开更多
Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic ...Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.展开更多
The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarr...The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.展开更多
Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of vario...Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of various tumors.However,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains unclear.This study was aimed to elucidate the effect of SENP3 in MCL.Methods The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or immunohistochemistry.MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs.Cell proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow cytometry.mRNA sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo.Results SENP3 was upregulated in MCL patient samples and cells.Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis.Meanwhile,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown.Furthermore,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model.Conclusion SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.展开更多
文摘SUMO化修饰是一种把小泛素相关修饰物(small ubiquition related modifier,SUMO)共价连接到细胞内靶蛋白半胱氨酸残基上的一种蛋白质翻译后修饰。SUMO化修饰参与并调控着多种细胞进程,如转录调控、核转运和信号转导等。SUMO化修饰是一种动态可逆的修饰方式。SUMO特异性蛋白酶(SUMO-specific proteases,SENPs)可以使SUMO化修饰的蛋白质发生去SUMO化,在维持细胞内SUMO化与去SUMO化的平衡中起重要作用。研究表明,SENPs与多种癌症的发生发展密切相关,如SENP1能直接调节多条致癌通路,诱发正常的前列腺上皮细胞状态异常。癌细胞中的SENP3能诱导血管生成。因此,对去SUMO化机制研究可以为开发癌症治疗药物提供新的思路。
基金supported by the National Natural Science Foundation of China(No.32370130).
文摘Microbial selenite(Se(Ⅳ)) reduction to elemental selenium nanoparticles(SeNPs) and chromate(Cr(Ⅵ)) remediation constitute effective detoxification processes. The strain Bacillus wiedmannii ES2-45 can efficiently reduce 5 mmol/L Se(Ⅳ) into SeNPs over 14 h and 1 mmol/L Cr(Ⅵ) within 36 h. Proteomic analysis and qRT-PCR revealed that reductases, including dithiol oxidoreductase(DsbA), Fe-S biosynthesis domain-containing protein(Fes),and aldose-6-phosphate reductase(Aldo), and bacillithiol(BSH) were involved in Se(Ⅳ) reduction. Heterologous expression further confirmed the Se(Ⅳ)-reducing function of three genes and enhanced the Se(Ⅳ) and Cr(Ⅵ) resistance ability. Moreover, the difference between Se(Ⅳ) treatments and controls both intra-and extra-cellular BSH concentration per biomass indicated that BSH contributes to Se(Ⅳ) reduction. Selenium-fortified rice was obtained by foliar spray of SeNPs synthesized by the strain ES2-45. To the best of our knowledge, DsbA and Aldo reductase were firstly verified for the role in Se(Ⅳ) reduction and Cr(Ⅵ)resistance. Importantly, it is a promising strategy that B. wiedmannii ES2-45 is served as an efficient bacterium for SeNP synthesis, selenium biofortification and heavy metal bioremediation.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.32070616 and 82170794).
文摘Background:Small ubiquitin-like modifier(SUMO)-specific proteases(SENPs)cleave the isopeptidic bond between SUMO1/2/3 and protein substrates,thus regulating the structure,activity,and lifetime of a variety of proteins.Recently,accumulating evidence has suggested that SENPs play a role in the initiation and progression of human cancers.Nevertheless,the potential role of the SENP family of proteins in liver cancer has yet to be fully elucidated.Methods:This study conducted a comprehensive bioinformatics analysis of the SENP family in liver cancer,including differential expression profiling,survival analysis,mutation and copy number variations(CNVs)assessment,immune infiltration and drug sensitivity correlation,functional enrichment analyses using data from The Cancer Genome Atlas(TCGA),Clinical Proteomic Tumor Analysis Consortium(CPTAC),LinkedOmics,and other public databases.Furthermore,we performed in vitro experiments using Huh-7 and Hep-3B cell lines to investigate the functional roles of SENP1 and SENP3 in hepatocellular carcinoma cell proliferation,colony formation,and migration.Results:Our results indicated that SENP1,3,and 7 were significantly overexpressed in liver hepatocellular carcinoma(LIHC).Elevated expressions of SENP1,3,and 7 are positively correlated with poor overall survival(OS)in LIHC patients.In addition,SENP1,3,and 7 expressions are related to immune infiltration and drug sensitivity.SENP1,3,and 7 co-expressed genes were enriched in mitochondrial function,ribosomal translation,and cell cycle control.Conclusion:SENP1,3,and 7 are prognostic biomarkers and potential therapeutic targets for LIHC.Knockdown of SENP1 and SENP3 inhibited the proliferation,clonogenicity,and migration of hepatocellular carcinoma cells.
基金supported by the National Science Fund for Excellent Young Scholars(NSFC-82322058)the Program of National Natural Science Foundation of China(NSFC-82103929,NSFC-82273713)+10 种基金the Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)the National Science Fund for Distinguished Young Scholars of Hubei Province of China(2023AFA046)the Fundamental Research Funds for the Central Universities(WHU:2042022kf1205)Fundamental Research Funds for the Central Universities(WHU:2042022kf1031)for Ying Zhuthe Fundamental Research Funds for the Central Universities(2042022rc0026,2042023kf1005)for Xiao-Ping Miaothe Knowledge Innovation Program of Wuhan(whkxjsj011,2023020201010073)for Jian-Bo Tianthe Science and Technology Innovation Seed Fund of Zhongnan Hospital of Wuhan University(znpy2019060)for Yong-Chang Weithe Distinguished Young Scholars of China(NSFC-81925032)the Key Program of National Natural Science Foundation of China(NSFC-82130098)the Youth Program of National Natural Science Foundation of China(NSFC-82003547)the Program of Health Commission of Hubei Province(WJ2023M045)。
文摘Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.
基金supported by Zanjan University of Medical Sciences,Zanjan,Iran(Grant Number:A-12-1244-16&Ethical Code:IR.ZUMS.REC.1399.316).
文摘The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.
基金supported by the Chongqing Natural Science Foundation(No.2023NSCQ-MSX3161 and No.cstc2020jcyj-msxmX1058)the National Natural Science Foundation of China(No.81800172).
文摘Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of various tumors.However,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains unclear.This study was aimed to elucidate the effect of SENP3 in MCL.Methods The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or immunohistochemistry.MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs.Cell proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow cytometry.mRNA sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo.Results SENP3 was upregulated in MCL patient samples and cells.Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis.Meanwhile,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown.Furthermore,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model.Conclusion SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.
