Stigma color is a critical agronomic trait in watermelon that plays an important role in pollination.However,there are few reports on the regulation of stigma color in watermelon.In this study,a genetic analysis of th...Stigma color is a critical agronomic trait in watermelon that plays an important role in pollination.However,there are few reports on the regulation of stigma color in watermelon.In this study,a genetic analysis of the F2 population derived from ZXG1553(P1,with orange stigma)and W1-17(P2,with yellow stigma)indicated that stigma color is a quantitative trait and the orange stigma is recessive compared with the yellow stigma.Bulk segregant analysis sequencing(BSA-seq)revealed a 3.75 Mb segment on chromosome 6 that is related to stigma color.Also,a major stable effective QTL Clqsc6.1(QTL stigma color)was detected in two years between cleaved amplified polymorphic sequencing(CAPS)markers Chr06_8338913 and Chr06_9344593 spanning a~1.01 Mb interval that harbors 51 annotated genes.Cla97C06G117020(annotated as zinc finger protein CONSTANS-LIKE 4)was identified as the best candidate gene for the stigma color trait through RNA-seq,quantitative real-time PCR(qRT-PCR),and gene structure alignment analysis among the natural watermelon panel.The expression level of Cla97C06G117020 in the orange stigma accession was lower than in the yellow stigma accessions with a significant difference.A nonsynonymous SNP site of the Cla97C06G117020 coding region that causes amino acid variation was related to the stigma color variation among nine watermelon accessions according to their re-sequencing data.Stigma color formation is often related to carotenoids,and we also found that the expression trend of ClCHYB(annotated asβ-carotene hydroxylase)in the carotenoid metabolic pathway was consistent with Cla97C06G117020,and it was expressed in low amounts in the orange stigma accession.These data indicated that Cla97C06G117020 and ClCHYB may interact to form the stigma color.This study provides a theoretical basis for gene fine mapping and mechanisms for the regulation of stigma color in watermelon.展开更多
Objective:Hepatocellular carcinoma(HCC)is a prevalent malignancy with poor survival.Different cell types in the tumor microenvironment participate in the tumorigenesis and progression of HCC.This study aimed to analyz...Objective:Hepatocellular carcinoma(HCC)is a prevalent malignancy with poor survival.Different cell types in the tumor microenvironment participate in the tumorigenesis and progression of HCC.This study aimed to analyze the immune microenvironment of HCC and its relationship with clinical outcomes.Methods:We analyzed HCC RNA-seq for cell type identification and prognosis by estimating relative subsets of RNA transcripts using CIBERSORTx.The interaction between B cells and macrophages in HCC was analyzed using a Hepa1-6 orthotopic transplantation mouse model and flow cytometry.The effect of Zinc finger protein 296(ZNF296)on the interaction of B cells and macrophages was verified using human HCC tissues analyzed through western blot,quantitative real-time polymerase chain reaction(qPCR),and multiplex immunofluorescence.A comparative analysis of immune cells associated with HCC prognosis was performed using RNA-seq data from The Cancer Genome Atlas(TCGA),bulk multimodal data,and single-cell transcriptomic data from existing HCC single-cell transcriptomic data employing the Single Cell Inferred Site Specific Omics Resource for Tumor Microenvironments(SCISSOR).Results:Liver hepatocellular carcinoma(LIHC)RNA-seq analysis of TCGA showed that high eosinophil infiltration promoted HCC progression.The proportion of B cells correlated with that of macrophages(r=−0.24)and affected the infiltration and programmed death ligand 1(PD-L1)expression of macrophages in HCC.ZNF296 may participate in the interaction between B cells and macrophages to accelerate the HCC progression by regulating PAFAH1B3 and H2AFX.Moreover,ZNF296 expression positively correlated with LAG3(r=0.27)and CTLA4(r=0.31)expression levels.Among the immune cell phenotypes related to survival and death identified by SCISSOR analysis,T cells correlated with an excellent prognosis of HCC.The normal function of liver and dendritic cells was also associated with a good prognosis in HCC.Conclusions:This study analyzed the interaction of the immune microenvironment with HCC prognosis,identifying ZNF296 as a promising diagnostic and therapeutic target for HCC.展开更多
AIM： To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats. METHODS： AIIogeneic liver transplantation from DA rats to Lewis rats was performed. Chronic liver allograft d...AIM： To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats. METHODS： AIIogeneic liver transplantation from DA rats to Lewis rats was performed. Chronic liver allograft dysfunction was induced in the rats by administering low-dose tacrolimus at postoperative day （POD） 5. Hepatic overexpression of A20 was achieved by recom- binant adenovirus （rAd.）-mediated gene transfer ad- ministered intravenously every 10 d starting from POD 10. The recipient rats were injected with physiologi- cal saline, rAdEasy-A20 （1 × 109 pfu/30 g weight） or rAdEasy （1 × 109 pfu/30 g weight） every 10 d through the tail vein for 3 mo starting from POD 10. Liver tissue samples were harvested on POD 30 and POD 60. RESULTS： Liver-transplanted rats treated with only tacrolimus showed chronic allograft dysfunction with severe hepatic fibrosis. A20 overexpression ameliorated the effects on liver function, attenuated liver allograft fibrosis and prolonged the survival of the recipient rats. Treatment with A20 suppressed hepatic protein pro- duction of tumor growth factor （TGF）-β1, interleukin- 113, caspase-8, CD40, CD40L, intercellular adhesion molecule-i, vascular cell adhesion molecule-1 and E-selectin. A20 treatment suppressed liver cell apopto- sis and inhibited nuclear factor-KB activation of Kupffer cells （KCs）, liver sinusoidal endothelial cells （LSECs） and hepatic stellate cells （HSCs）, and it subsequently decreased cytokine mRNA expression in KCs and LSECs and reduced the production of TGF-β1 in HSCs. CONCLUSION： A20 might prevent chronic liver allogra- ft dysfunction by re-establishing functional homeostasis of KCs, LSECs and HSCs.展开更多
Zinc finger protein（ZFP） genes comprise a large and diverse gene family, and are involved in biotic and abiotic stress responses in plants. In this study, a total of 126 ZFP genes classified into various types in wh...Zinc finger protein（ZFP） genes comprise a large and diverse gene family, and are involved in biotic and abiotic stress responses in plants. In this study, a total of 126 ZFP genes classified into various types in wheat were characterized and subjected to expression pattern analysis under inorganic phosphate（Pi） deprivation. The wheat ZFP genes and their corresponding GenBank numbers were obtained from the information of a 4×44K wheat gene expression microarray chip. They were confirmed by sequence similarity analysis and named based on their homologs in Brachypodium distachyon or Oriza sativa. Expression analysis based on the microarray chip revealed that these ZFP genes are categorized into 11 classes according to their gene expression patterns in a 24-h of Pi deprivation regime. Among them, ten genes were differentially up-regulated, ten genes differentially downregulated, and two genes both differentially up- and down-regulated by Pi deprivation. The differentially up- or down-regulated genes exhibited significantly more or less transcripts at one, two, or all of the checking time points（1, 6, and 24 h） of Pi stress in comparison with those of normal growth, respectively. The both differentially up- and down-regulated genes exhibited contrasting expression patterns, of these, TaWRKY70;5 showed significantly up-regulated at 1 and 6 h and down-regulated at 24 h whereas TaAN1AN20-8;2 displayed significantly upregulated at 1 h and downregulated at 6 h under deprivation Pi condition. Real time PCR analysis confirmed the expression patterns of the differentially expressed genes obtained by the microarray chip. Our results indicate that numerous ZFP genes in wheat respond to Pi deprivation and have provided further insight into the molecular basis that plants respond to Pi deprivation mediated by the ZFP gene family.展开更多
The zinc finger proteins belong to the largest family of transcription factors.But there is little research of Cys2/His2 type zinc finger proteins in cotton,and there is no submission of correlating
C2H2-type zinc finger proteins （ZFPs） are thought to play important roles in modulating the responses of plants to drought, salinity and oxidative stress. However, direct evidence is lacking for the involvement of t...C2H2-type zinc finger proteins （ZFPs） are thought to play important roles in modulating the responses of plants to drought, salinity and oxidative stress. However, direct evidence is lacking for the involvement of these ZFPs in abscisic acid （ABA）-induced antioxidant defense in plants. In this study, the role of the rice （Oryza sativa L. sub.japonica cv. Nipponbare） C2H2-type ZFP ZFP182 in ABA-induced antioxidant defense and the relationship between ZFP182 and two rice MAPKs, OsMPK1 and OsMPK5 in ABA signaling were investigated. ABA treatment induced the increases in the expression of ZFP182, OsMPK1 and OsMPK5, and the activities of superoxide dismutase （SOD） and ascorbate peroxidase （APX） in rice leaves. The transient gene expression analysis and the transient RNA interference （RNAi） analysis in protoplasts showed that ZFP182, OsMPK1 and OsMPK5 are involved in ABA-induced up-regulation in the activities of SOD and APX. Besides, OsMPK1 and OsMPK5 were shown to be required for the up-regulation in the expression of ZFP182 in ABA signaling, but ZFP182 did not mediate the ABA-induced up-regulation in the expression of OsMPK1 and OsMPKS. These results indicate that ZFP182 is required for ABA-induced antioxidant defense and the expression of ZFP182 is regulated by rice MAPKs in ABA signaling.展开更多
The plant hormone auxin plays a crucial role in lateral root development. To better understand the rnolecular mechanisms underlying lateral root formation, an auxin-responsive gene OsCYP2 （Oso2g0121300） was characte...The plant hormone auxin plays a crucial role in lateral root development. To better understand the rnolecular mechanisms underlying lateral root formation, an auxin-responsive gene OsCYP2 （Oso2g0121300） was characterized from rice. Compared to the wild type, OsCYP2-RNAi （RNA interference） lines exhibited distinctive defects in lateral root development. Yeast two-hybrid and glutathione S-transferase puIl-down results confirmed that OsCYP2 interacted with a C2HC-type zinc finger protein （OsZFP, O501g0252900） which is located in the rice nucleus. T2OsZFP-RNAi lines had significantly fewer lateral roots than did wild-type plants, which suggests a role for OsCYP2 and OsZFP in regulating lateral root development.Quantitative real-time polymerase chain reaction showed that the expression of certain Aux/IAA （auxin/indole-3- acetic acid） genes was altered in OsCYP2- and OsZFP-RNAi lines in response to IAA. These findings imply that OsCYP2 and OsZFP participate in IAA signal pathways controlling lateral root development. More importantly, OslAA11 showed functional redundancy not only in OsCYP2-RNAi lines but also in OsZFP-RNAi lines, which provides important clues for the elucidation of mechanisms controlling lateral root development in response to auxin.展开更多
Cell fate determination is a basic developmental process during the growth of multicellular organisms.Trichomes and root hairs of Arabidopsis are both readily accessible structures originating from the epidermal cells...Cell fate determination is a basic developmental process during the growth of multicellular organisms.Trichomes and root hairs of Arabidopsis are both readily accessible structures originating from the epidermal cells of the aerial tissues and roots respectively, and they serve as excellent models for understanding the molecular mechanisms controlling cell fate determination and cell morphogenesis. The regulation of trichome and root hair formationis a complex program that consists of the integration of hormonal signals with a large number of transcriptional factors, including MYB and b HLH transcriptional factors.Studies during recent years have uncovered an important role of C2H2 type zinc finger proteins in the regulation of epidermal cell fate determination. Here in this minireview we briefly summarize the involvement of C2H2 zinc finger proteins in the control of trichome and root hair formation in Arabidopsis.展开更多
Fruit size is largely defined by the number and size of cells in the fruit.Endoreduplication–a specialized cell cycle–is highly associated with cell expansion during tomato fruit growth.However,how endoreduplication...Fruit size is largely defined by the number and size of cells in the fruit.Endoreduplication–a specialized cell cycle–is highly associated with cell expansion during tomato fruit growth.However,how endoreduplication coupled with cell size is regulated remains poorly understood.In this study,we identified a zinc finger gene SlPZF1(Solanum lycopersicum PERICARP-ASSOCIATED ZINC FINGER PROTEIN 1)that was highly expressed in the pericarp of developing fruits.Plants with altered SlPZF1 expression produced smaller fruits due to the reduction in cell size associated with weakened endoreduplication.Overexpressing SlPZF1 delayed cell division phase by enhancing early expression of several key cell cycle regulators including SlCYCD3;1 and two plant specific mitotic cyclin-dependent protein kinase(SlCDKB1 and SlCDKB2)in the pericarp tissue.Furthermore,we identified 14 putative SlPZF1 interacting proteins(PZFIs)via yeast two hybrid screening.Several PZFIs,including Pre-mRNA-splicing factor(SlSMP1/PZFI4),PAPA-1-like conserved region family protein(PZFI6),Fanconi anemia complex components(PZFI3 and PZFI10)and bHLH transcription factor LONESOME HIGHWAY(SILHW/PZFI14),are putatively involved in cell cycle regulation.Our results demonstrate that fruit growth in tomato requires balanced expression of the novel cell size regulator SlPZF1.展开更多
ZINC finger proteins play an important role in the regulation of gene expression by binding to DNA/RNA in a sequence-specific manner. Now nearly 200 human zinc finger genes have been cloned. According to the differenc...ZINC finger proteins play an important role in the regulation of gene expression by binding to DNA/RNA in a sequence-specific manner. Now nearly 200 human zinc finger genes have been cloned. According to the difference of the conservative domain, the zinc finger proteins can be classified into several types.Most of zinc finger proteins belong to the C<sub>2</sub>H<sub>2</sub> type containing the consensus amino acid sequence YECX<sub>2</sub>CX<sub>3</sub>FX<sub>5</sub>LX<sub>2</sub>HX<sub>3</sub>HTGEKP, which is rather conservative especially in the link region between two zinc finger motifs （TGEKP）展开更多
Non-alcoholic fatty liver disease(NAFLD)is a common chronic disease characterized by excessive fat accumulation in hepatocytes in the absence of alcohol consumption.Modern trends towards excessive calorie intake and s...Non-alcoholic fatty liver disease(NAFLD)is a common chronic disease characterized by excessive fat accumulation in hepatocytes in the absence of alcohol consumption.Modern trends towards excessive calorie intake and sedentary life styles have increased the prevalence of NAFLD accompanied by obesity and type 2 diabetes.However,the molecular mechanisms underlying the initiation and progression of NAFLD are not clear.Zinc finger proteins(ZFPs)are a superfamily of metalloproteins that contain zinc finger motifs.ZFPs play diverse physiological roles in tissue homeostasis and also contribute to many pathological conditions,including metabolic,cardiovascular,and neurodegenerative diseases and various types of cancer.In this review,we highlight our current knowledge of several ZFPs that play critical roles in the progression of NAFLD,describe their mechanistic functional networks,and discuss the potential for ZFPs as therapeutic targets for NAFLD.展开更多
ZNE191 is a new zine finger gene which has a 1107 bp open reading frame (ORF) and encodes a 368amino acid protein including a putative DNA-binding domain of four Cys2His2, zine finder motifs at its C-terminal region. ...ZNE191 is a new zine finger gene which has a 1107 bp open reading frame (ORF) and encodes a 368amino acid protein including a putative DNA-binding domain of four Cys2His2, zine finder motifs at its C-terminal region. The ZNF191 eDNA is located in the chromosome 18q12.1 region where it is known that a variety of hereditary diseases arc related to. Probably, this protein has potential function of stimulating the gene transcription.In order to examine the function and structure of ZNF191 protein, the OHK of ZNf191 and its zinc finger region ZNF191 (243-368) genes were inserted into PTSA-18 expression vector by PCR amplification, then the constructed genes were expressed in the PTSA-18/B121 (DE3) system. The two proteins were purified by DEAE-52, CM-23 and Heparin-Sepharose 4B columns. The pooled proteins showed a single band as assayed by Coomasie Brillian Blue Staining of an SDS/polyacryamide gel.展开更多
The zinc finger motif was used as a vehicle for the initial discovery of Ikaros in the context of T-cell differentiation and has been central to all subsequent analyses of Ikaros function.The Ikaros gene is alternatel...The zinc finger motif was used as a vehicle for the initial discovery of Ikaros in the context of T-cell differentiation and has been central to all subsequent analyses of Ikaros function.The Ikaros gene is alternately spliced to produce several isoforms that confer diversity of function and consequently have complicated analysis of the function of Ikaros in vivo.Key features of Ikaros in vivo function are associated with six C2H2 zinc fingers;four of which are alternately incorporated in the production of the various Ikaros isoforms.Although no complete structures are available for the Ikaros protein or any of its family members,considerable evidence has accumulated about the structure of zinc fingers and the role that this structure plays in the functions of the Ikaros family of proteins.This review summarizes the structural aspects of Ikaros zinc fingers,individually,and in tandem to provide a structural context for Ikaros function and to provide a structural basis to inform the design of future experiments with Ikaros and its family members.展开更多
BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness o...BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.展开更多
Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women’s health.The precise mechanism underlying the development of UCEC remains elusive.Zinc finger pr...Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women’s health.The precise mechanism underlying the development of UCEC remains elusive.Zinc finger protein 554(ZNF554),a member of the Krüppel-associated box domain zinc finger protein superfamily,was reported to be dysregulated in various illnesses,including malignant tumors.This study aimed to examine the involvement of ZNF554 in the development of UCEC.Methods:The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay.Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection.CCK-8,wound healing,and Transwell invasion assays were employed to assess cell proliferation,migration,and invasion.Propidium iodide(PI)staining combined with fluorescence-activated cell sorting(FACS)flow cytometer was utilized to detect cell cycle distribution.qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels.Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5(RBM5).Results:The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines.Decreased expression of ZNF554 was associated with higher tumor stage,decreased overall survival,and reduced disease-free survival in UCEC.ZNF554 overexpression suppressed cell proliferation,migration,and invasion,while also inducing cell cycle arrest.In contrast,a decrease in ZNF554 expression resulted in the opposite effect.Mechanistically,ZNF554 transcriptionally regulated RBM5,leading to the deactivation of the Wingless(WNT)/β-catenin signaling pathway.Moreover,the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression onβ-catenin and p-glycogen synthase kinase-3β(p-GSK-3β).Similarly,the deliberate activation of RBM5 reduced the increase inβ-catenin and p-GSK-3βcaused by the suppression of ZNF554.In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown.Additionally,when RBM5 was overexpressed,it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels.Conclusion:ZNF554 functions as a tumor suppressor in UCEC.Furthermore,ZNF554 regulates UCEC progression through the RBM5/WNT/β-catenin signaling pathway.ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.展开更多
基金supported by fundings from the Natural Science Funds for Outstanding Youth of Heilongjiang Province,China(YQ2022C011)the National Natural Science Foundation of China(32172577)+2 种基金the China Agriculture Research System of MOF and MARA,China(CARS-25)the Taishan Industrial Leading Talents Project,China(LJNY202112)the Natural Science Foundation of Heilongjiang Province,China(LH2022C025).
文摘Stigma color is a critical agronomic trait in watermelon that plays an important role in pollination.However,there are few reports on the regulation of stigma color in watermelon.In this study,a genetic analysis of the F2 population derived from ZXG1553(P1,with orange stigma)and W1-17(P2,with yellow stigma)indicated that stigma color is a quantitative trait and the orange stigma is recessive compared with the yellow stigma.Bulk segregant analysis sequencing(BSA-seq)revealed a 3.75 Mb segment on chromosome 6 that is related to stigma color.Also,a major stable effective QTL Clqsc6.1(QTL stigma color)was detected in two years between cleaved amplified polymorphic sequencing(CAPS)markers Chr06_8338913 and Chr06_9344593 spanning a~1.01 Mb interval that harbors 51 annotated genes.Cla97C06G117020(annotated as zinc finger protein CONSTANS-LIKE 4)was identified as the best candidate gene for the stigma color trait through RNA-seq,quantitative real-time PCR(qRT-PCR),and gene structure alignment analysis among the natural watermelon panel.The expression level of Cla97C06G117020 in the orange stigma accession was lower than in the yellow stigma accessions with a significant difference.A nonsynonymous SNP site of the Cla97C06G117020 coding region that causes amino acid variation was related to the stigma color variation among nine watermelon accessions according to their re-sequencing data.Stigma color formation is often related to carotenoids,and we also found that the expression trend of ClCHYB(annotated asβ-carotene hydroxylase)in the carotenoid metabolic pathway was consistent with Cla97C06G117020,and it was expressed in low amounts in the orange stigma accession.These data indicated that Cla97C06G117020 and ClCHYB may interact to form the stigma color.This study provides a theoretical basis for gene fine mapping and mechanisms for the regulation of stigma color in watermelon.
基金the Key Program of the National Natural Science Foundation of China(No.81930016)National Natural Science Foundation of China(No.92159202 and No.82273177)+1 种基金Key Research and Development Plan of Zhejiang Province(No.2021C03118 and No.2022C03108)Zhejiang Provincial Natural Science Foundation of China(No.LQ20H160029).
文摘Objective:Hepatocellular carcinoma(HCC)is a prevalent malignancy with poor survival.Different cell types in the tumor microenvironment participate in the tumorigenesis and progression of HCC.This study aimed to analyze the immune microenvironment of HCC and its relationship with clinical outcomes.Methods:We analyzed HCC RNA-seq for cell type identification and prognosis by estimating relative subsets of RNA transcripts using CIBERSORTx.The interaction between B cells and macrophages in HCC was analyzed using a Hepa1-6 orthotopic transplantation mouse model and flow cytometry.The effect of Zinc finger protein 296(ZNF296)on the interaction of B cells and macrophages was verified using human HCC tissues analyzed through western blot,quantitative real-time polymerase chain reaction(qPCR),and multiplex immunofluorescence.A comparative analysis of immune cells associated with HCC prognosis was performed using RNA-seq data from The Cancer Genome Atlas(TCGA),bulk multimodal data,and single-cell transcriptomic data from existing HCC single-cell transcriptomic data employing the Single Cell Inferred Site Specific Omics Resource for Tumor Microenvironments(SCISSOR).Results:Liver hepatocellular carcinoma(LIHC)RNA-seq analysis of TCGA showed that high eosinophil infiltration promoted HCC progression.The proportion of B cells correlated with that of macrophages(r=−0.24)and affected the infiltration and programmed death ligand 1(PD-L1)expression of macrophages in HCC.ZNF296 may participate in the interaction between B cells and macrophages to accelerate the HCC progression by regulating PAFAH1B3 and H2AFX.Moreover,ZNF296 expression positively correlated with LAG3(r=0.27)and CTLA4(r=0.31)expression levels.Among the immune cell phenotypes related to survival and death identified by SCISSOR analysis,T cells correlated with an excellent prognosis of HCC.The normal function of liver and dendritic cells was also associated with a good prognosis in HCC.Conclusions:This study analyzed the interaction of the immune microenvironment with HCC prognosis,identifying ZNF296 as a promising diagnostic and therapeutic target for HCC.
基金Supported by The National Natural Science Foundation of China,No.30872529the PhD Program Fund of the Ministry of Education of China,No.20030610078the Chinese Postdoctoral Science Foundation,No.2003033531
文摘AIM： To investigate the effect of zinc finger protein A20 on chronic liver allograft dysfunction in rats. METHODS： AIIogeneic liver transplantation from DA rats to Lewis rats was performed. Chronic liver allograft dysfunction was induced in the rats by administering low-dose tacrolimus at postoperative day （POD） 5. Hepatic overexpression of A20 was achieved by recom- binant adenovirus （rAd.）-mediated gene transfer ad- ministered intravenously every 10 d starting from POD 10. The recipient rats were injected with physiologi- cal saline, rAdEasy-A20 （1 × 109 pfu/30 g weight） or rAdEasy （1 × 109 pfu/30 g weight） every 10 d through the tail vein for 3 mo starting from POD 10. Liver tissue samples were harvested on POD 30 and POD 60. RESULTS： Liver-transplanted rats treated with only tacrolimus showed chronic allograft dysfunction with severe hepatic fibrosis. A20 overexpression ameliorated the effects on liver function, attenuated liver allograft fibrosis and prolonged the survival of the recipient rats. Treatment with A20 suppressed hepatic protein pro- duction of tumor growth factor （TGF）-β1, interleukin- 113, caspase-8, CD40, CD40L, intercellular adhesion molecule-i, vascular cell adhesion molecule-1 and E-selectin. A20 treatment suppressed liver cell apopto- sis and inhibited nuclear factor-KB activation of Kupffer cells （KCs）, liver sinusoidal endothelial cells （LSECs） and hepatic stellate cells （HSCs）, and it subsequently decreased cytokine mRNA expression in KCs and LSECs and reduced the production of TGF-β1 in HSCs. CONCLUSION： A20 might prevent chronic liver allogra- ft dysfunction by re-establishing functional homeostasis of KCs, LSECs and HSCs.
基金supported by the National Natural Science Foundation of China (31201674 and 31371618)the Natural Science Foundation of Hebei Province, China (C2011204031)the Key Laboratory of Crop Growth Regulation of Hebei Province, China
文摘Zinc finger protein（ZFP） genes comprise a large and diverse gene family, and are involved in biotic and abiotic stress responses in plants. In this study, a total of 126 ZFP genes classified into various types in wheat were characterized and subjected to expression pattern analysis under inorganic phosphate（Pi） deprivation. The wheat ZFP genes and their corresponding GenBank numbers were obtained from the information of a 4×44K wheat gene expression microarray chip. They were confirmed by sequence similarity analysis and named based on their homologs in Brachypodium distachyon or Oriza sativa. Expression analysis based on the microarray chip revealed that these ZFP genes are categorized into 11 classes according to their gene expression patterns in a 24-h of Pi deprivation regime. Among them, ten genes were differentially up-regulated, ten genes differentially downregulated, and two genes both differentially up- and down-regulated by Pi deprivation. The differentially up- or down-regulated genes exhibited significantly more or less transcripts at one, two, or all of the checking time points（1, 6, and 24 h） of Pi stress in comparison with those of normal growth, respectively. The both differentially up- and down-regulated genes exhibited contrasting expression patterns, of these, TaWRKY70;5 showed significantly up-regulated at 1 and 6 h and down-regulated at 24 h whereas TaAN1AN20-8;2 displayed significantly upregulated at 1 h and downregulated at 6 h under deprivation Pi condition. Real time PCR analysis confirmed the expression patterns of the differentially expressed genes obtained by the microarray chip. Our results indicate that numerous ZFP genes in wheat respond to Pi deprivation and have provided further insight into the molecular basis that plants respond to Pi deprivation mediated by the ZFP gene family.
基金Supported by National Natural Science Foundation of China,No.81072033 and No.81372580Natural Science Foundation of Hebei Province,No.C2010000619+1 种基金Extra Characteristic Foundation of Colleges and Universities in Hebei Province,No.[2005]52the Health Department of Hebei Province,No.20110460
文摘AIM: To investigate the expression of zinc finger protein 139 (ZNF139) in gastric cancer (GC), and to analyze its clinical significance.
文摘The zinc finger proteins belong to the largest family of transcription factors.But there is little research of Cys2/His2 type zinc finger proteins in cotton,and there is no submission of correlating
基金supported by the National Basic Research Program of China (2012CB114306)the National Natural Science Foundation of China (90717108, 30700491, 30970238, 31070254, and 31071344)+5 种基金the Fundamental Research Funds for the Central Universities (KYZ200905, KYT201001, and KYZ201157)the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutionsthe Natural Science Foundation of Jiangsu Province (BK2010455)the Research Fund for the Doctoral Program of Higher Education of China (20090097110017)the Program for New Century Excellent Talents in University (NCET-10-0498)the Grant from the Education Department of Jiangsu (200910)
文摘C2H2-type zinc finger proteins （ZFPs） are thought to play important roles in modulating the responses of plants to drought, salinity and oxidative stress. However, direct evidence is lacking for the involvement of these ZFPs in abscisic acid （ABA）-induced antioxidant defense in plants. In this study, the role of the rice （Oryza sativa L. sub.japonica cv. Nipponbare） C2H2-type ZFP ZFP182 in ABA-induced antioxidant defense and the relationship between ZFP182 and two rice MAPKs, OsMPK1 and OsMPK5 in ABA signaling were investigated. ABA treatment induced the increases in the expression of ZFP182, OsMPK1 and OsMPK5, and the activities of superoxide dismutase （SOD） and ascorbate peroxidase （APX） in rice leaves. The transient gene expression analysis and the transient RNA interference （RNAi） analysis in protoplasts showed that ZFP182, OsMPK1 and OsMPK5 are involved in ABA-induced up-regulation in the activities of SOD and APX. Besides, OsMPK1 and OsMPK5 were shown to be required for the up-regulation in the expression of ZFP182 in ABA signaling, but ZFP182 did not mediate the ABA-induced up-regulation in the expression of OsMPK1 and OsMPKS. These results indicate that ZFP182 is required for ABA-induced antioxidant defense and the expression of ZFP182 is regulated by rice MAPKs in ABA signaling.
基金supported by the Special Fund for Agroscientific Research in the Public Interest(201303022)National Natural Science Foundation of China(31301272,31570434)+1 种基金the Fund from Zhejiang A&F University(2013FR022)Zhejiang Provincial Top Key Discipline of Biology and its Open Foundation(2015D19)
文摘The plant hormone auxin plays a crucial role in lateral root development. To better understand the rnolecular mechanisms underlying lateral root formation, an auxin-responsive gene OsCYP2 （Oso2g0121300） was characterized from rice. Compared to the wild type, OsCYP2-RNAi （RNA interference） lines exhibited distinctive defects in lateral root development. Yeast two-hybrid and glutathione S-transferase puIl-down results confirmed that OsCYP2 interacted with a C2HC-type zinc finger protein （OsZFP, O501g0252900） which is located in the rice nucleus. T2OsZFP-RNAi lines had significantly fewer lateral roots than did wild-type plants, which suggests a role for OsCYP2 and OsZFP in regulating lateral root development.Quantitative real-time polymerase chain reaction showed that the expression of certain Aux/IAA （auxin/indole-3- acetic acid） genes was altered in OsCYP2- and OsZFP-RNAi lines in response to IAA. These findings imply that OsCYP2 and OsZFP participate in IAA signal pathways controlling lateral root development. More importantly, OslAA11 showed functional redundancy not only in OsCYP2-RNAi lines but also in OsZFP-RNAi lines, which provides important clues for the elucidation of mechanisms controlling lateral root development in response to auxin.
基金supported by National Natural Science Foundation of China (Grant Nos. 31370215, 31228002 and 31970167)International Scientific and Technological Cooperation Project of Science and Technology Department of Zhejiang Province (Grant No. 2013C24007)+1 种基金Zhejiang Provincial Natural Science Foundation of China (Grant No. Z3110004)Ph.D.Programs Foundation of Ministry of Education of China (Grant No. 20120101110079)
文摘Cell fate determination is a basic developmental process during the growth of multicellular organisms.Trichomes and root hairs of Arabidopsis are both readily accessible structures originating from the epidermal cells of the aerial tissues and roots respectively, and they serve as excellent models for understanding the molecular mechanisms controlling cell fate determination and cell morphogenesis. The regulation of trichome and root hair formationis a complex program that consists of the integration of hormonal signals with a large number of transcriptional factors, including MYB and b HLH transcriptional factors.Studies during recent years have uncovered an important role of C2H2 type zinc finger proteins in the regulation of epidermal cell fate determination. Here in this minireview we briefly summarize the involvement of C2H2 zinc finger proteins in the control of trichome and root hair formation in Arabidopsis.
基金The work was supported by National Key Research and Development Program of China(2016YFD0101900)the National Natural Science Foundation of China(31672164)Agriculture and Rural Affairs Commission of Shanghai municipality(Agriculture Applied Technology Development Program,HuNongKeGong Grant No.2015-6-1-7).
文摘Fruit size is largely defined by the number and size of cells in the fruit.Endoreduplication–a specialized cell cycle–is highly associated with cell expansion during tomato fruit growth.However,how endoreduplication coupled with cell size is regulated remains poorly understood.In this study,we identified a zinc finger gene SlPZF1(Solanum lycopersicum PERICARP-ASSOCIATED ZINC FINGER PROTEIN 1)that was highly expressed in the pericarp of developing fruits.Plants with altered SlPZF1 expression produced smaller fruits due to the reduction in cell size associated with weakened endoreduplication.Overexpressing SlPZF1 delayed cell division phase by enhancing early expression of several key cell cycle regulators including SlCYCD3;1 and two plant specific mitotic cyclin-dependent protein kinase(SlCDKB1 and SlCDKB2)in the pericarp tissue.Furthermore,we identified 14 putative SlPZF1 interacting proteins(PZFIs)via yeast two hybrid screening.Several PZFIs,including Pre-mRNA-splicing factor(SlSMP1/PZFI4),PAPA-1-like conserved region family protein(PZFI6),Fanconi anemia complex components(PZFI3 and PZFI10)and bHLH transcription factor LONESOME HIGHWAY(SILHW/PZFI14),are putatively involved in cell cycle regulation.Our results demonstrate that fruit growth in tomato requires balanced expression of the novel cell size regulator SlPZF1.
文摘ZINC finger proteins play an important role in the regulation of gene expression by binding to DNA/RNA in a sequence-specific manner. Now nearly 200 human zinc finger genes have been cloned. According to the difference of the conservative domain, the zinc finger proteins can be classified into several types.Most of zinc finger proteins belong to the C<sub>2</sub>H<sub>2</sub> type containing the consensus amino acid sequence YECX<sub>2</sub>CX<sub>3</sub>FX<sub>5</sub>LX<sub>2</sub>HX<sub>3</sub>HTGEKP, which is rather conservative especially in the link region between two zinc finger motifs （TGEKP）
基金This work was supported by funds from the National Natural Science Foundation of China(31770840 to X.Ma and 31800989 to L.Xu)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(TP2017042 to X.Ma)。
文摘Non-alcoholic fatty liver disease(NAFLD)is a common chronic disease characterized by excessive fat accumulation in hepatocytes in the absence of alcohol consumption.Modern trends towards excessive calorie intake and sedentary life styles have increased the prevalence of NAFLD accompanied by obesity and type 2 diabetes.However,the molecular mechanisms underlying the initiation and progression of NAFLD are not clear.Zinc finger proteins(ZFPs)are a superfamily of metalloproteins that contain zinc finger motifs.ZFPs play diverse physiological roles in tissue homeostasis and also contribute to many pathological conditions,including metabolic,cardiovascular,and neurodegenerative diseases and various types of cancer.In this review,we highlight our current knowledge of several ZFPs that play critical roles in the progression of NAFLD,describe their mechanistic functional networks,and discuss the potential for ZFPs as therapeutic targets for NAFLD.
基金Project supported by the National Natural Science Foundation of China (Grant No. 29671008).
文摘ZNE191 is a new zine finger gene which has a 1107 bp open reading frame (ORF) and encodes a 368amino acid protein including a putative DNA-binding domain of four Cys2His2, zine finder motifs at its C-terminal region. The ZNF191 eDNA is located in the chromosome 18q12.1 region where it is known that a variety of hereditary diseases arc related to. Probably, this protein has potential function of stimulating the gene transcription.In order to examine the function and structure of ZNF191 protein, the OHK of ZNf191 and its zinc finger region ZNF191 (243-368) genes were inserted into PTSA-18 expression vector by PCR amplification, then the constructed genes were expressed in the PTSA-18/B121 (DE3) system. The two proteins were purified by DEAE-52, CM-23 and Heparin-Sepharose 4B columns. The pooled proteins showed a single band as assayed by Coomasie Brillian Blue Staining of an SDS/polyacryamide gel.
文摘The zinc finger motif was used as a vehicle for the initial discovery of Ikaros in the context of T-cell differentiation and has been central to all subsequent analyses of Ikaros function.The Ikaros gene is alternately spliced to produce several isoforms that confer diversity of function and consequently have complicated analysis of the function of Ikaros in vivo.Key features of Ikaros in vivo function are associated with six C2H2 zinc fingers;four of which are alternately incorporated in the production of the various Ikaros isoforms.Although no complete structures are available for the Ikaros protein or any of its family members,considerable evidence has accumulated about the structure of zinc fingers and the role that this structure plays in the functions of the Ikaros family of proteins.This review summarizes the structural aspects of Ikaros zinc fingers,individually,and in tandem to provide a structural context for Ikaros function and to provide a structural basis to inform the design of future experiments with Ikaros and its family members.
基金Supported by Hebei Provincial Health Commission Youth Science and Technology Project,No.20210027.
文摘BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality globally.Resistance to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient outcomes.Long noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain unclear.AIM To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance.METHODS Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance.Various bioinformatics tools were employed to elucidate molecular mechanisms.The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction.Functional assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA alterations.Interactions between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream pathways.Additionally,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance.RESULTS LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)expression.PRNT was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 expression.Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing resistance.Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT.The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo.CONCLUSION The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184.This regulatory mechanism enhances CRC progression and resistance to oxaliplatin,positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.
基金supported by the Science-Technology Foundation for Middle-aged and Young Scientists of Wannan Medical College(No.WK2021F19)the 2023 Wannan Medical College Research Fund(No.WK2023ZZD18).
文摘Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women’s health.The precise mechanism underlying the development of UCEC remains elusive.Zinc finger protein 554(ZNF554),a member of the Krüppel-associated box domain zinc finger protein superfamily,was reported to be dysregulated in various illnesses,including malignant tumors.This study aimed to examine the involvement of ZNF554 in the development of UCEC.Methods:The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay.Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection.CCK-8,wound healing,and Transwell invasion assays were employed to assess cell proliferation,migration,and invasion.Propidium iodide(PI)staining combined with fluorescence-activated cell sorting(FACS)flow cytometer was utilized to detect cell cycle distribution.qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels.Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5(RBM5).Results:The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines.Decreased expression of ZNF554 was associated with higher tumor stage,decreased overall survival,and reduced disease-free survival in UCEC.ZNF554 overexpression suppressed cell proliferation,migration,and invasion,while also inducing cell cycle arrest.In contrast,a decrease in ZNF554 expression resulted in the opposite effect.Mechanistically,ZNF554 transcriptionally regulated RBM5,leading to the deactivation of the Wingless(WNT)/β-catenin signaling pathway.Moreover,the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression onβ-catenin and p-glycogen synthase kinase-3β(p-GSK-3β).Similarly,the deliberate activation of RBM5 reduced the increase inβ-catenin and p-GSK-3βcaused by the suppression of ZNF554.In vitro experiments showed that ZNF554 overexpression-induced decreases in cell proliferation and migration were counteracted by RBM5 knockdown.Additionally,when RBM5 was overexpressed,it hindered the improvements in cell proliferation and migration caused by reducing the ZNF554 levels.Conclusion:ZNF554 functions as a tumor suppressor in UCEC.Furthermore,ZNF554 regulates UCEC progression through the RBM5/WNT/β-catenin signaling pathway.ZNF554 shows a promise as both a prognostic biomarker and a therapeutic target for UCEC.
