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Objective:To investigate the expression of zinc finger protein 22 (ZNF22) gene in hepatocellular carcinoma (HCC) and its effect on tumor proliferation, apoptosis, invasion and metastasis of HCC.Methods:The expression of ZNF22 in 32 HCC specimens, and 371 HCC samples from the cancer genome atlas database were analyzed. ZNF22 knockdown and negative control SNU-449 and JHH-7 HCC cell lines were constructed. The effects of ZNF22 on HCC cells were observed by cell proliferation assay, plate clone formation assay, apoptosis assay, scratch healing assay, Transwell invasion assay, subcutaneous tumor formation, tail vein injection transfer, and small animal live imaging assay in nude mice.Results:The expression of ZNF22 gene is higher in HCC tissues than in paracellular carcinoma tissues, and the difference was statistically significant ( P<0.001). The growth rate of SNU-449 and JHH-7 cells in ZNF22 knockdown group was lower than that in control group, and the difference was statistically significant ( P<0.001). Compared with negative control group, the clone number formed by SNU-449 cells in ZNF22 knockdown group decreased (26±8 vs. 59±5, P<0.01), the level of apoptosis increased (6.60%±0.22% vs. 2.38%±0.30%, P<0.001), the migration rate decreased (14.47%±6.42% vs. 68.84%±8.01%, P<0.001), and the number of invasive cells decreased (48.00±2.23 vs. 179.00±4.81, P<0.001). There was no obvious tumor growth after subcutaneous injection of JHH-7 cells into nude mice in ZNF22 knockdown group, and the systemic fluorescence expression was lower than that of the negative control group, and the difference was statistically significant ( P<0.05). No metastases were observed on autopsy in knockdown group nude mice. Conclusion:ZNF22 is highly expressed in HCC while knockdowing ZNF22 gene inhibited the growth, proliferation, invasion, metastasis of HCC cells, and induced apoptosis of HCC cells.
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Objective:To investigate the expression levels and clinical significance of glioma-associated oncogene homolog 1 (GLI1) and sonic hedgehog signaling molecule (Shh) in the malignant transformation of ovarian endometriosis (EM).Methods:The expressions of GLI1 and Shh were detected by real-time reverse transcription (RT)-polymerase chain reaction (PCR) and EnVision method in 50 cases of ovarian EM tissues, 35 cases of atypical endometriosis (aEM) and 50 cases of endometriosis-associated ovarian cancer (EAOC). The expression differences of two molecular markers in the malignant transformation of ovarian EM were compared, and the relationships between two molecular markers and the clinicopathological features and prognosis of EAOC were analyzed.Results:(1) RT-PCR showed that the expression levels of GLI1 mRNA in EM, aEM and EAOC group were 1.77±0.40, 3.54±0.44, and 7.80±0.24, respectively. The expression levels of Shh mRNA were 0.95±0.21, 3.14±0.35, and 5.41±0.31, respectively. GLI1 and Shh mRNA in EAOC group were significantly higher than those in EM and aEM group (all P<0.01), and there were statistically significant differences between EM and aEM group (all P<0.01). The percentages of GLI1 in ovarian EM, aEM and EAOC were 32% (16/50), 57% (20/35), and 66% (33/50), respectively, meanwhile, the positive expression rates of Shh were 20% (10/50), 49% (17/35), and 54% (27/50), respectively (all P<0.01). GLI1 mRNA expression was positively correlated with Shh mRNA expression in EAOC tissues ( r=0.721, P<0.01). The expressions of GLI1 protein were proportionated to Shh protein in EAOC tissues ( r=0.608, P=0.001). (2) The expression of GLI1 was significantly related to the International Federation of Gynecology and Obstetrics (FIGO) stage, cancer antigen 125 (CA 125) levels, lymph node metastasis, and Platinum resistance in EAOC patients (all P<0.05). The expression of Shh were related to FIGO stage and lymph node metastasis in EAOC patients (all P<0.05). Logistic regression analysis showed that GLI1 expression was an independent risk factor for poor prognosis in EAOC patients ( P<0.05). Kaplan-meier survival analysis showed that the overall survival rate of EAOC patients with high GLI1 expression and low GLI1 expression was 12.1% and 35.3%, respectively, with statistical significance ( χ2=10.73, P<0.01). The overall survival rate of EAOC patients with high and low expression of Shh protein was 11.1% and 30.4%, in which there was statistically significant difference ( χ2=3.96, P=0.047). Conclusion:GLI1 and Shh are highly associated with the malignant transformation of ovarian EM, which may play a role in promoting malignant degeneration of ovarian EM, and the high expression of GLI1 and Shh indicates a poor prognosis in EAOC patients.
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Objective:To investigate the expression of the zinc finger protein 18 (ZNF18) in the pancreatic ductal adenocarcinoma (PDAC) tissue and analyze its relationship with the clinicopathological features and prognosis.Methods:Cancer tissue specimens from 131 patients with PDAC who were surgically resected and pathologically confirmed at First Affiliated Hospital of Naval Medical University from March 2017 to December 2019 were collected. ZNF18 protein expression in cancer tissue was detected by immunohistochemical staining, and high and low ZNF18 expression groups were divided based on the expression level of ZNF18. . Kaplan-Meier method and Log-Rank test were used to analyze the relationship between ZNF18 expression level and overall survival rate of PDAC patients. Furthermore, the correlation between ZNF18 protein expression level and clinicopathological features was analyzed, and the Cox regression hazards model was applied for the univariate and multivariate analysis of the factors affecting the prognosis of PDAC patients.Results:82 of 131(62.60%) PDAC tissues had high ZNF18 expression, and 49(37.40%) PDAC tissues had low ZNF18 expression; the survival time in the high ZNF18 expression group was significantly higher than that in the low ZNF18 expression group (21.53±0.69 months vs 12.17±1.57 months), and the difference was statistically significant( P<0.001). Low ZNF18 expression in PDAC was associated with lymph node metastasis( P<0.05), but was not correlated with gender, age, tumor location, tumor volume, differentiation degree, TNM stage, nerve invasion, and vascular cancer thrombus. The results of the univariate analysis showed that tumor differentiation degree, TNM stage, lymph node metastasis, and ZNF18 expression were all associated with the prognosis of PDAC patients. The results of the multivariate analysis showed that tumor differentiation degree( HR=0.463, 95% CI 0.279-0.769, P=0.003), lymph node metastasis( HR=2.062, 95% CI 1.247-3.409, P=0.005), and ZNF18 expression( HR=0.416, 95% CI 0.255-0.676, P<0.001) were independent risk factors affecting the prognosis of patients with PDAC. Conclusions:Low ZNF18 expression in PDAC tissues was closely associated with lymph node metastasis and poor prognosis. ZNF18 can be used as an important molecular marker to evaluate the prognostic survival of PDAC patients.
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Objective:To compare the efficacy of sakubatril valsartan and valsartan in the treatment of patients with chronic cardiac insufficiency and the influence on zinc finger protein A20 and nuclear factor-κB (NF-κB) in peripheral bloodmononuclear cells (PBMCs).Methods:Ninety-senven patients with chronic cardiac insufficiency admitted to the Affiliated Hospital of Jining Medical College from February 2019 to January 2020 were continuously selected and randomly divided into the control group (48 cases) and the observation group (49 cases). Both groups received routine anti-heart failure according to the guidelines. The control group added with valsartan and the observation group added with sakubatril valsartan treatment. Before the treatment and after 3 months of treatment, the changes of cardiac function indexes and the changes of inflammatory markers such as hypersensitive C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), matrix metalloproteinase 9 (MMP-9), and N-terminal pro B-type natriuretic peptide (NT-proBNP) were compared. PBMCs was extracted to detect zinc finger protein A20 and NF-κB levels. The incidence of adverse reactions in the two groups was recorded, and the relationship between zinc finger proteins A20, NF-κB and the myocardial injury marker NT-proBNP were analyzed.Results:After 3 months of treatment, the changes of cardiac function indexes in the observation group were better than those in the control group and the levels of hs-CRP, TNF-α, MMP-9, NT-proBNP in the observation group were lower than those in the control group: (1.96 ± 0.57) mg/L vs. (2.87 ± 0.79) mg/L, (7.11 ± 1.46) μg/L vs. (8.24 ± 1.57) μg/L, (110.14 ± 10.63) μg/L vs. (129.52 ± 17.96) μg/L, (716.91 ± 105.78) ng/L vs. (965.25 ± 97.41) ng/L, there were statistical differences ( P<0.05). After 3 months of treatment, the levels of finger protein A20, NF-κB in the observation group were lower than those in the control group: (3.57 ± 1.13) % vs. (4.41 ± 1.32) %, (29.87 ± 6.58) ng/L vs. (35.71 ± 10.02) ng/L, there were statistical differences ( P<0.05). Finger protein A20 and NF-κB in patients with chronic cardiac insufficiency were positively correlated with NT-proBNP ( r = 0.487, 0.738, P<0.01). Conclusions:On the basis of conventional treatment, compared with valsartan, the addition of sakubatril valsartan, can improve the cardiac function of patients with chronic cardiac insufficiency, reduce the body′s inflammatory response, reduce the expression of myocardial injury marker NT-proBNP, inhibit the activation of PBMCs NF-κB, and reduce the level offinger protein A20.
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SBP-box genes are a class of plant-specific transcription factors which have a common DNA-binding domain(SBP-domain) with an unusual zinc-finger architecture. Many of the genes in this class are thought to play adevelopmental role and a few are involved in the determination of plant architecture. We have made acomparative study of these genes in the genomes of rice (Oryza sativa japonica and Oryza sativa indica) andits nine siblings using a recently proposed hybrid method for orthology and paralogy detection (HyPPO).According to HyPPO, the SBP-box proteins of rice siblings could be divided into twenty primary orthologousgroups on the basis of their overall sequence features. This contrasts with a much less number of groups foundin earlier work with other plant genomes using phylogenetic analysis of the SBP-domains only. The orthologous groups reported by HyPPO showed close correspondence in exon–intron structure and motif conservation. Comparison between different Oryza species revealed disparity in the maintenance of orthologousgenes which may result in their different developmental characteristics. Inclusion of the SBP-box proteins fromA. thaliana did not result in any change in the orthologous groups except for the A. thaliana proteins beingadded to some of the existing groups. The closer correspondence between the proteins in the primaryorthologous clusters is expected to help in a more reliable prediction of their functions. It is also expected toprovide better insight into the evolutionary history of this class of plant-specific proteins.
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There are complex mechanisms in the development and progression of hepatocellular carcinoma, which have not been fully clarified at present. Zinc finger protein family is the largest transcription factor family in human genome, and more and more evidence has shown that zinc finger proteins play an important role in the development and progression of hepatocellular carcinoma and are expected to become new tumor biomarkers and therapeutic targets for hepatocellular carcinoma. This article reviews the structure and biological functions of zinc finger proteins and their role and regulatory mechanisms in hepatocellular carcinoma.
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OBJECTIVE@#To investigate the expression of ZNF652 in breast cancer tissues and cells and explore its role in breast cancer cell proliferation, invasion and migration.@*METHODS@#We exploited the data from the TCGA database to analyze the differential expression of ZNF652 in breast cancer tissues and adjacent tissues and the correlations of ZNF652 expression with the clinicopathological characteristics of breast cancer patients including molecular subtypes, pathological types, TNM stages and clinical stages. RT-qPCR and Western blotting were used to detect the expression of ZNF652 in 5 breast cancer cell lines including MCF-7, MDA-MB-231, SK-BR-3, UACC-812 and BT-474. Using a lentivirus system and siRNA technique, we assessed the effects of ZNF652 over-expression and knockdown on proliferation, colony forming ability, migration and invasion of breast cancer cells with CCK-8 assay, clonogenic assay, Transwell assay and wound healing assay. The subcellular localization of ZNF652 in 293T cells was determined using immunofluorescence assay.@*RESULTS@#ZNF652 was significantly up-regulated in breast cancer tissues (@*CONCLUSIONS@#ZNF652 is highly expressed in breast cancer tissues and cells to promote the development and progression of breast cancer and may serve as a potential molecular target for diagnosis and treatment of the malignancy.
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Humans , Breast Neoplasms/genetics , Carcinogenesis , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, NeoplasticABSTRACT
ZNF804A rs1344706 has been identified as one of the risk genes for schizophrenia. However, the neural mechanisms underlying this association are unknown. Given that ZNF804A upregulates the expression of COMT, we hypothesized that ZNF804A may influence brain activity by interacting with COMT. Here, we genotyped ZNF804A rs1344706 and COMT rs4680 in 218 healthy Chinese participants. Amplitudes of low-frequency fluctuations (ALFFs) were applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680. The ALFFs of the bilateral dorsolateral prefrontal cortex showed a significant ZNF804A rs1344706 × COMT rs4680 interaction, manifesting as a U-shaped modulation, presumably by dopamine signaling. Significant main effects were also found. These findings suggest that ZNF804A affects the resting-state functional activation by interacting with COMT, and may improve our understanding of the neurobiological effects of ZNF804A and its association with schizophrenia.
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Objective To investigate the relationship between three polymorphic sites of ZNF804A gene and cognitive dysfunction in schizophrenia.Methods Polymerase Chain Reaction (PCR) was used to determine the genotypes and allele frequencies of the three sites (rs1344706,rs12613195 and rs1583048) of ZNF804A gene in 320 patients with schizophrenia (case group) and 324 normal people (control group).The Montreal Cognitive Assessment (MoCA) was used to assess cognitive function.Results (1) The allelic and genotypic distributions in rs1344706 between patients with schizophrenia (T/T,T/G,G/G genotypes:20.3％,50.0％,29.7％),and healthy controls(T/T,T/G,G/G genotypes:13.7％,51.2％,35.1％)had statistically significance(P＞0.05).There was a statistically significant difference in the allele and genotype distribution of rs1344706 between the case group and the control group (P＜0.05),and the family transmission disequilibrium existed in rs1344706 and rs12613195.(2) The MoCA scores in the case group(＜26 points) were lower than those of the control group (P＜0.05).(3)There was a statistically significant difference between the total scores of MoCA (F=202.49,P＜0.05) and scores assessed in different time (F=53.34,P＜ 0.05) in patients with three genotypes of rs1344706.Moreover,the interaction between genotype and time was also statistically significant (F=3.88,P＜0.05),in which the patients with T/T genotype had the lowest total score.(4)There was a statistically significant difference between the total score of MoCA(F=367.78,P ＜0.05) and scores assessed in different time (F=27.35,P＜0.05) in patients with three genotypes of rs12613195,in which the patients with C/C genotype had the lowest total score.However,the interaction between genotype and time was not statistically significant(P＞0.05).(5)The effect of rs1344706 on cognitive function was slightly larger than that of rs12613195.(6)The cognitive function scores of patients carrying rs1344706 and rs12613195 sites decreased year by year.Conclusion ZNF804A gene rs1344706 and rs12613195 may be associated with cognitive dysfunction of schizophrenia,and rs1344706T and rs12613195C may be risk factors for schizophrenia and cognitive impairment.Furthermore,cognitive impairment in patients with rs1344706 is more pronounced and worsened with prolonged condition.rs1583048 may not be associated with cognitive function of schizophrenia.
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Objective: To observe the effect of Weichang'an on the tumor growth and lymph node metastasis, and RUN and FYVE domain-containing protein 3(RUFY3),Zinc finger protein 1(SNAI1),vascular endothelial growth factor(VEGF),epithelial-mesenchymal transition(EMT)-related proteins in nude mice with subcutaneous xenograft tumor human gastric carcinoma MKN45, so as to discuss the mechanism of Weichang'an on MKN45 human gastric metastasis. Method: The nude mice model of human gastric carcinoma MKN45 cells was established and randomly divided into normal saline group (0.5 mL/mouse), Weichang'an granule group (3.54 g·kg-1) and Weichang'an decoction group (35.49 g·kg-1). The tumor weight and volume of axillary lymph nodes in each group were observed. The morphology of lymph nodes in each group was detected by hematoxylin-eosin (HE) staining. The expressions of related proteins were detected by immunohistochemistry, including RUFY3,SNAI1,VEGF,E-cadherin,N-cadherin,Vimentin. Result: Compared with the normal saline group, the tumor weight and volume of axillary lymph node were decreased (PPPConclusion: Both Weichang'an granule and Weichang'an decoction can inhibit the tumor growth and metastasis of axillary lymph nodes, obviously down-regulate the expressions of RUFY3,SNAI1,VEGF,N-cadherin,Vimentin and up-regulate the expression of E-cadherin in human gastric MKN45 subcutaneous transplanted tumor in nude mice. This suggested that Weichang'an may inhibit the tumor metastasis through regulation expressions of RUFY3,SNAI1,VEGF and EMT-related proteins.
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Trichoderma reesei Rut-C30 is widely used in industrial cellulase production, and development of cellulase hyper-producer is of great importance for economic lignocellulosic biorefinery. In this study, T. reesei Rut-C30 was engineered with an artificial zinc finger proteins (AZFPs) library. Two mutants T. reesei M1 and M2 with improved cellulase production were obtained. Compared to the parent strain, the filter paper activity (FPase) of T. reesei M1 and M2 increased 100% and 53%, respectively. In addition, the total amount of extracellular protein from the M1 mutant increased 69%, whereas the endo-β-glucanase (CMCase) activity of the M2 mutant is 64% higher compared to the parental strain. Furthermore, RT-qPCR analysis showed that the major cellulase genes exhibited significantly increased expression in both mutants, but different patterns were observed in the two mutants. On the other hand, the cellulase transcriptional repressor ace1 was down-regulated in both mutants, but the transcription level of the activator xyr1 was only up-regulated in the strain M1. These results demonstrated that different AZFPs exert diverse regulatory mechanisms on cellulase production in T. reesei. Analysis of the target genes of AZFPs from T. reesei M1 and M2 will not only benefit further exploration of the regulatory mechanisms of cellulase biosynthesis in T. reesei, but also enable development of cellulase hyper-producing strains by metabolic engineering.
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Cellulase , Gene Library , Transcription Factors , Trichoderma , Zinc FingersABSTRACT
Objective@#To investigate the effect of PR domain zinc finger protein 9 (PRDM9), one of the histone methylated transferases, on osteogenic differentiation ability of periodontal ligament mesenchymal stem cells (PDLSC).@*Methods@#PDLSC with PRDM9 gene knocked down by PRDM9 shRNA using recombinant lentiviral vector were allocated into the PRDM9sh group, and the transfected shRNA was as the control group. The gene expression efficiency was evaluated by reverse transcription polymerase chain reaction (RT-PCR). Alkaline phosphatase activity (ALP), alizarin red staining, mineralization and osteocalcin, which belongs to osteogenic differentiation markers detected by RT-PCR and Western blotting to detect the osteogenic differentiation ability of stem cells from periodontal ligaments in vitro. In vivo, PRDM9sh and control group cells was transplanted into the dorsal dermal to explore the osteogenesis. The area percentage of new osteogenic tissue was calculated by image pro software and statistically analyzed.@*Results@#RT-PCR results showed that the relative expression of PRDM9 gene in PRDM9sh (0.460±0.017) was significantly lower than that in control group (1.000±0.107) (P<0.05). The results of ALP activity determined at 5 days postinduction in a significant decrease in PRDM9sh cells (0.762±0.063) compared with control group (1.225±0.058) (P<0.01). Alizarin red staining induced by osteogenesis at 2 weeks and 3 weeks showed that the staining of PRDM9sh was significantly lighter than that in control group. Quantitative calcium analysis results showed that the calcium ion concentration induced by osteogenesis at 2 weeks and 3 weeks [(0.071±0.004), (0.075±0.001)] in PRDM9sh was significantly lower than that in control group at 2 weeks and 3 weeks [(0.282±0.006), (0.485+0.004)] (P<0.01). RT-PCR results showed that the relative expression of osteocalcin mRNA in PRDM9sh (1.059±0.148) was significantly lower than that in control group at 2 weeks (2.542±0.190) (P<0.01). Western blotting results showed that osteocalcin expression in PRDM9sh was significantly lower than that in control group at 1 and 2 weeks after osteogenesis induction. Animal transplantation experiments results indicated that PRDM9 significantly inhibited the osteogenesis of PDLSC in vivo, and the proportion of osteogenic area calculated showed that the osteogenic capacity of PRDM9sh [(3.8±2.41)%] was significantly lower than that in control group [(24.54±7.06)%](P<0.05).@*Conclusions@#Depletion of PRDM9 repressed the osteogenic differentiation of stem cells from periodontal ligament in vitro and in vivo.
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Objective@#To investigate the effect of hepatitis B virus (HBV) X gene integration on expression of zinc finger protein ZBTB20 in chronic hepatitis B (CHB) patients complicated with hepatocellular carcinoma (HCC).@*Methods@#Eighteen CHB patients complicated with HCC who underwent surgical treatment in Taizhou Enze Medical Center Enze Hospital and Taizhou Central Hospital from July 2015 to June 2017 were enrolled. Samples of carcinoma tissue, para-carcinoma tissue and corresponding normal liver tissue were collected from each case. DNA was extracted from three kinds of tissue samples. HBV-Alu-polymerase chain reaction (PCR) was used to amplify the integrated HBVX fragments and their bilateral flanking sequences in human genomic DNA. The integrated HBV fragments were determined by PCR products sequencing. Protein was extracted from three kinds of tissue samples.The level of expression of ZBTB20 was detected by protein imprinting. Statistical analysis was performed using t test, analysis of variance, and χ2 test.@*Results@#Among the 18 CHB patients complicated with HCC, integration of HBVX gene was found in 13 carcinoma tissue samples, 16 para-carcinoma tissue samples and 9 corresponding normal liver tissue samples. The difference was statistically significant (χ2=6.353, P=0.037). Of the 18 patients, the protein expressions of ZBTB20 in carcinoma tissue, para-carcinoma tissue and corresponding normal tissue were (50.14±11.25)%, (40.71±7.17)% and (39.06±5.17)%, respectively, which was statistically different (F=9.420, P<0.01). HBVX gene integration was detected at ZBTB20 locus in five patients. The expression levels of ZBTB20 in patients with HBVX gene integration at this locus in carcinoma tissue, para-carcinoma tissue and corresponding, normal liver tissue were all significantly lower than those in patients without HBVX gene integration (carcinoma tissue (37.37±10.30)% vs (55.06±7.06)%, para-carcinoma tissue (32.06±2.61)% vs (44.04±5.24)%, corresponding normal tissue (34.66±5.59)% vs (40.76±4.04)%, t=4.205, 4.821 and 2.589, respectively, all P<0.05).@*Conclusions@#Incidence of HBVX integration in para-carcinoma tissue is higher than that in carcinoma tissue in CHB patients complicated with HCC.The expression level of ZBTB20 in carcinoma tissue is higher than that in para-carcinoma tissue. Integration of HBVX gene at ZBTB20 locus may decreases the expression of ZBTB20.
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Objective To investigate the effect of hepatitis B virus (HBV) X gene integration on expression of zinc finger protein ZBTB20 in chronic hepatitis B (CHB) patients complicated with hepatocellular carcinoma (HCC).Methods Eighteen CHB patients complicated with HCC who underwent surgical treatment in Taizhou Enze Medical Center Enze Hospital and Taizhou Central Hospital from July 2015 to June 2017 were enrolled.Samples of carcinoma tissue,para-carcinoma tissue and corresponding normal liver tissue were collected from each case.DNA was extracted from three kinds of tissue samples.HBV-Alu-polymerase chain reaction (PCR) was used to amplify the integrated HBVX fragments and their bilateral flanking sequences in human genomic DNA.The integrated HBV fragments were determined by PCR products sequencing.Protein was extracted from three kinds of tissue samples.The level of expression of ZBTB20 was detected by protein imprinting.Statistical analysis was performed using t test,analysis of variance,and x2 test.Results Among the 18 CHB patients complicated with HCC,integration of HBVX gene was found in 13 carcinoma tissue samples,16 para-carcinoma tissue samples and 9 corresponding normal liver tissue samples.The difference was statistically significant (x2 =6.353,P =0.037).Of the 18 patients,the protein expressions of ZBTB20 in carcinoma tissue,para-carcinoma tissue and corresponding normal tissue were (50.14 ± 11.25)％,(40.71±7.17) ％ and (39.06 ± 5.17) ％,respectively,which was statistically different (F =9.420,P ＜ 0.01).HBVX gene integration was detected at ZBTB20 locus in five patients.The expression levels of ZBTB20 in patients with HBVX gene integration at this locus in carcinoma tissue,para-carcinoma tissue and corresponding,normal liver tissue were all significantly lower than those in patients without HBVX gene integration (carcinoma tissue (37.37±10.30)％ vs (55.06 ± 7.06)％,para-carcinoma tissue (32.06 ± 2.61)％ vs (44.04 ± 5.24)％,corresponding normal tissue (34.66 ±5.59)％ vs (40.76 ±4.04)％,t--4.205,4.821 and 2.589,respectively,all P ＜0.05).Conclusions Incidence of HBVX integration in para-carcinoma tissue is higher than that in carcinoma tissue in CHB patients complicated with HCC.The expression level of ZBTB20 in carcinoma tissue is higher than that in para-carcinoma tissue.Integration of HBVX gene at ZBTB20 locus may decreases the expression of ZBTB20.
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Objective To explore the expression of zinc finger protein 217 (ZNF217) in non-small cell lung cancer (NSCLC) and its correlation with prognosis of patients. Methods A total of 120 NSCLC patients in Chongqing Three Gorges Central Hospital from January 2012 to October 2013 were selected. Immunohistochemical method was used to test the expression of ZNF217 in NSCLC tissues and paracancerous tissues. The correlation of ZNF217 expression with patient's clinicopathological features was analyzed. At the same time, the Kaplan-Meier method and Cox regression model multiple factor analysis method were used to explore the factors affecting the prognosis of patients after NSCLC radical operations. Results ZNF217 mainly existed in cell nucleus of NSCLC. The positive expression rate of ZNF217 in the cancer tissues was higher than that in the paracancerous tissues [52.5％ (63/120) vs. 20.1％ (25/120), χ 2 = 25.909, P < 0.05]. The positive expression rate of ZNF217 increased with the increase of tumor T stage (χ 2 = 7.333, P = 0.026), N stage (χ 2 = 7.782, P = 0.020) and TNM stage (χ 2 = 11.557, P = 0.003). The overall survival (P = 0.007) and progression-free survival (P = 0.004) of patients with positive ZNF217 were poorer than those of patients with negative ZNF217. Cox multiple factor analysis showed that ZNF217 was an independent risk factor affecting the prognosis of NSCLC. Conclusion ZNF217 is an independent risk factor affecting the prognosis of NSCLC, and it may be a potential target for accurate treatment of NSCLC.
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Hepatocellular carcinoma is one of the most common malignant tumors in the world,and its morbidity and mortality have been high.The current preferred treatment for hepatocellular carcinoma is surgical treatment and liver transplantation,but the 5-year survival rate is still low.Due to the insidious onset of hepatocellular carcinoma,most patients have no special manifestations at the initial stage.At the time of diagnosis,they are already in the terminal stage and lose the opportunity of surgery.The Hh pathway plays a key role in the development of tumors.The zinc finger protein GLi plays an important role in tumorigenesis as a key transcription factor in the Hh pathway.At the same time,zinc finger protein GLi can play a key role in the invasion and metastasis of hepatocellular carcinoma by inducing epithelial-mesenchymal transition.In addition,the zinc finger protein GLi also interacts with various tumor-related factors to affect the occurrence and development and treatment of hepatocellular carcinoma.This article reviews the role of zinc finger protein GLi in the development and treatment of hepatocellular carcinoma.
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Esophageal cancer is one of the common malignant tumors in China.Although it is currently treated by multidisciplinary treatment,esophageal cancer's prognosis is still poor.The occurrence of esophageal cancer is closely related to the metabolism of trace element zinc.Zinc deficiency can induce the development of esophageal cancer by inducing inflammatory reaction and microRNAs imbalance.Zinc ion can play an important role in esophageal cancer by regulating the activity of ion channel.The formed zinc finger protein can function as an oncogene or a tumor suppressor gene in esophageal cancer.Zinc metabolism is accompanied by complex biological changes in the pathogenesis of esophageal cancer,and multiple mechanisms interact and are closely linked.The article reviews the research results of recent years on the mechanism of zinc deficiency,zinc ion-regulated ion channel and zinc finger protein in the development of esophageal cancer.
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@#Normal embryonic development is regulated by different genes and related signaling pathways. In recent years, the association between different genes and genes, genes and signaling pathways in the same organization has been widely concerned by scholars at home and abroad. Sp and Wnt gene deletion or mutation can lead to abnormal embryonic development. The results of this review indicate that abnormal embryonic development is due to Sp gene deletion/mutation The zinc finger protein superfamily member Sp1-9 is involved in the development of various tissues and organs , such as the hematopoietic system, respiratory system and skeletal system, and its deletion or mutation can lead to developmental abnormalities in embryonic tissues. In addition, the Sp8 gene is associated with the occurrence of cleft palate. By summarizing the observations about the relationship between the Wnt gene and cleft lip and palate in recent years, we can understand the abnormal expression of Wnt3, Wnt3A, Wnt5A, Wnt9B, Wnt10A and Wnt11 in humans. The occurrence of cleft lip and palate is closely related; Sp5/8 is a key downstream effector of the Wnt signaling pathway during embryonic development and participates in the Wnt signaling pathway. Sp5/8 and the Wnt signaling pathway are involved in the regulation of normal neural crest development and the self-renewal of embryonic stem cells in embryonic mice. In summary, this paper proposes that the Sp and Wnt genes may be involved in the regulation of the formation and occurrence of embryonic cleft palate and provides a reference for further study of the associated mechanisms between the two genes in the cleft palate model.
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Background: Jatropha curcas L., as an important strategic biofuel resource with considerable economic potential, has attracted worldwide attention. However, J. curcas has yet to be domesticated. Plant height, an important agronomic trait of J. curcas, has not been sufficiently improved, and the genetic regulation of this trait in J. curcas is not fully understood. Zinc finger proteins (ZFPs), a class of transcription factors, have previously been shown to play critical roles in regulating multiple aspects of plant growth and development and may accordingly be implicated in the genetic regulation of plant height in J. curcas. Results: In this study, we cloned JcZFP8, a C2H2 ZFP gene in J. curcas. We found that the JcZFP8 protein was localized in the nucleus and contained a conserved QALGGH motif in its C2H2 structure. Furthermore, ectopic expression of JcZFP8 under the control of the 35S promoter in transgenic tobacco resulted in dwarf plants with malformed leaves. However, when JcZFP8 was knocked out, the transgenic tobacco did not show the dwarf phenotype. After treatment with the gibberellic acid (GA) biosynthesis inhibitor paclobutrazol (PAC), the dwarf phenotype was more severe than plants that did not receive the PAC treatment, whereas application of exogenous gibberellin3 (GA3) reduced the dwarf phenotype in transgenic plants. Conclusions: The results of this study indicate that JcZFP8 may play a role in J. curcas plant phenotype through GA-related pathways. Our findings may help us to understand the genetic regulation of plant development in J. curcas and to accelerate breeding progress through engineering of the GA metabolic pathway in this plant. How to cite: Shi X,Wu Y, Dai T, et al. JcZFP8, a C2H2 zinc-finger protein gene from Jatropha curcas, influences plant development in transgenic tobacco.
Subject(s)
Tobacco/genetics , Jatropha , Plant Development , CYS2-HIS2 Zinc Fingers/genetics , Plant Growth Regulators/genetics , Transcription Factors , Triazoles , Plants, Genetically Modified/growth & development , Cloning, Molecular , Gene Expression Regulation, Plant , Real-Time Polymerase Chain Reaction , GibberellinsABSTRACT
Objective To investigate the effects of microRNA-1291 (miR-1291) on the expression of Zinc finger protein 8 (PHF8) gene in renal cell carcinoma and its effect on cell cycle and proliferation of renal cell carcinoma.Methods Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-1291 in renal cell carcinoma cell lines OS-RC-2,ACHN,A498,786-O and human proximal tubular epithelial cells HK-2.miR-1291 (miR-1291 group) and miR-NC (miR-NC group) were transfected into the renal cell lines with the lowest expression of miR-1291.qRT-PCR was used to detect the expression of miR-1291 and PHF8 mRNA in the transfected cells.The expression levels of PHF8,Cyclin-dependent kinase 6 (CDK6) and Cyclin D1 were detected by Western blotting.The effect of miR-1291 on the transcriptional activity of PHF8 was detected by double luciferase reporter gene system.Flow cytometry was used to detect cell cycle distribution.Methyl thiazolyl tetrazolium (MTT) assay and colony formation assay were used to detect cell viability and proliferation.Results The expressions of miR-1291 in renal carcinoma cell lines OS-RC-2,ACHN,A498,786-O and human proximal renal tubular epithelial cell HK-2 were 0.64 ± 0.17,0.60 ±0.15,0.29 ±0.08,0.63 ±0.08 and 1.01 ±0.17 respectively,with a significant difference (F=13.790,P ＜ 0.001).Compared with renal carcinoma cell lines OS-RC-2,ACHN and 786-O,the expression level of miR-1291 in A498 cell line was the lowest (P =0.002,P =0.006,P =0.003).The expression levels of miR-1291 in A498 cell lines of miR-NC group and miR-1291 group were 1.00 ± 0.03 and 775.25 ± 329.91 respectively,with a significant difference (t =4.694,P =0.003);and the expression levels of PHF8 mRNA were 1.00 ±0.11 and 0.57 ±0.18 respectively,with a significant difference (t =4.122,P =0.006).The results of Western blotting were consistent with the results of qRT-PCR,and the expressions of CDK6 and Cyclin D1 were significantly decreased.The double luciferase reporter gene showed that miR-1291could directly inhibit the activity of luciferase in the 3'un-translated region of target gene PHF8.Compared with miR-NC group,the proportion of renal carcinoma cells in S phase (23.40 ± 4.29 vs.32.19 ± 2.64;t =3.491,P =0.013) and G2-M phase (14.38 ± 4.05 vs.25.59 ± 6.01;t =3.095,P =0.021) decreased;and the proportion of cells in G0-G1 phase increased (62.22 ± 7.56 vs.42.22 ± 5.23,t =4.351,P =0.005).MTT assay showed that the cell viability of miR-1291 was significantly decreased.Colony formation experiments showed that the numbers of colonies formed by A498 cells in miR-NC group and miR-1291 group were 246.64 ± 39.94 and 87.34 ± 21.93 respectively,with a significant difference (t =6.993,P ＜ 0.001).Conclusion The expression of miR-1291 is significantly decreased in renal cancer cell lines.miR-1291 can significantly inhibit the proliferation of renal cell carcinoma cells by targeting interfering PHF8 gene expression,which may contribute to the development of new renal cancer target.