Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
Bromodomain(BRD)-containing proteins are central mediators of gene regulation,serving as key components of chromatin remodeling complexes and histone recognition scaffolds.By specifically recognizing acetylated lysine...Bromodomain(BRD)-containing proteins are central mediators of gene regulation,serving as key components of chromatin remodeling complexes and histone recognition scaffolds.By specifically recognizing acetylated lysine residues on histones(Kac)via their conserved BRD,these proteins influence chromatin structure and gene expression.Although their overarching role is well-established,the precise molecular functions and mechanisms of individual BRD proteins remain incompletely characterized.The ciliate Tetrahymena thermophila,a unicellular eukaryote with a transcriptionally active macronucleus enriched in histone acetylation,is an excellent model for exploring the significance of BRD-containing proteins.In this comprehensive review,all BRD-containing proteins encoded in the T.thermophila genome are systematically examined,including their expression profiles,histone acetylation targets,interacting proteins,and potential roles.This review lays the groundwork for future investigations into the complex roles of BRD proteins in chromatin remodeling and transcription regulation,offering insights into basic eukaryotic biology and the molecular mechanisms underlying BRD-linked diseases.展开更多
OBJECTIVE To discover a small-molecule bromodomain-containing protein 4(BRD4)inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer and exploreits potential mech...OBJECTIVE To discover a small-molecule bromodomain-containing protein 4(BRD4)inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer and exploreits potential mechanisms.METHODS BRD4 interactors were analyzed by PPI network prediction and The Cancer Genome Atlas(TCGA)analysis.The interaction between BRD4 and AMPK was confirmed by co-immunoprecipitation assay.Novel BRD4 inhibitors were designed and synthesized based upon pharmacophore analysis of BRD4(1),then screened by antiproliferative activity and Alpha Screen of BRD4(1).The selectivity of the best candidate compound 8f was validated by co-crystallization,FRET assay and co-immuno precipitation assay.The mechanisms of 8f were investigated by fluorescence microscopy,electron microscopy,Western blotting,immunocytochemistry,si RNA and GFP-m RFP-LC3 plasmid transfections,as well as immunohistochemistry and immunofluorescence.Potential mechanisms were discovered by i TRAQ-based proteomics analysis and the therapeutic effect of 8f was assessed by xenograft breast cancer mouse and zebrafish models.RESULTS We identified that BRD4 interacted with AMPK,which was remarkably downregulated in breast cancer.We next designed and synthesized 49 candidate compounds,and eventually discovered a selective small-molecule inhibitor of BRD4(8f).Subsequently,8f was discovered to induce autophagyassociated cell death(ACD)by BRD4-AMPK interaction,and thus activating AMPK-m TOR-ULK1-modulated autophagic pathway in breast cancer cells.Interestingly,the i TRAQ-based proteomics analyses revealed that 8f induced ACD pathways,involved in HMGB1,VDAC1/2 and e EF2.Moreover,8f displayed a therapeutic potential on both xenograft breast cancer mouse and zebrafish models.CONCLUSION We discovered a novel small-molecule inhibitor of BRD4 that induces BRD4-AMPK-modulated ACD in breast cancer,which may provide a candidate drug for future cancer therapy.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC),the predominant type of esophageal cancer,has a 5-year survival rate less than 20%.Although the cause of poor prognosis is the high incidence and mortality of ESCC,t...BACKGROUND Esophageal squamous cell carcinoma(ESCC),the predominant type of esophageal cancer,has a 5-year survival rate less than 20%.Although the cause of poor prognosis is the high incidence and mortality of ESCC,the high rate of metastasis after esophageal cancer surgery is the main cause of death after the surgery.Bromodomain-containing protein 4(BRD4),an epigenetic reader of chromatinacetylated histones in tumorigenesis and development,plays an essential role in regulating oncogene expression.BRD4 inhibition and BRD4 inhibition-based treatment can potentially suppress ESCC growth.However,the effects and mechanisms of action of BRD4 on ESCC cell migration remain unclear.AIM To explore the effect of BRD4 on cell migration of ESCC in vitro and its possible molecular mechanism.METHODS Human ESCC cell lines KYSE-450 and KYSE-150 were used.The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay was performed to examine cell proliferation,and the transwell migration assay was conducted to test ESCC cell migration.JQ1,a BRD4 inhibitor,was applied to cells,and BRD4 siRNA was transfected into ESCC cells to knockdown endogenous BRD4.GFP-RFP-LC3 adenovirus was infected into ESCC cells to evaluate the effect of JQ1 on autophagy.Western blotting was performed to determine the protein levels of BRD4,E-cadherin,vimentin,AMP-activated protein kinase(AMPK),and p-AMPK.RESULTS BRD4 was either downregulated by small interfering RNA or pretreated with JQ1 in ESCC cells,leading to increased tumor migration in ESCC cells in a dose-and time-dependent manner.Inhibition of BRD4 not only significantly suppressed cell proliferation but also strongly increased cell migration by inducing epithelial-mesenchymal transition(EMT).The protein expression of vimentin was increased and E-cadherin decreased in a dose-dependent manner,subsequently promoting autophagy in KYSE-450 and KYSE-150 cells.Pretreatment with JQ1,a BRD4 inhibitor,inhibited BRD4-induced LC3-II activation and upregulated AMPK phosphorylation in a dosedependent manner.Additionally,an increased number of autophagosomes and autolysosomes were observed in JQ1-treated ESCC cells.The autophagy inhibitor 3-methyladenine(3-MA)reversed the effects of BRD4 knockdown on ESCC cell migration and blocked JQ1-induced cell migration.3-MA also downregulated the expression of vimentin and upregulation E-cadherin.CONCLUSION BRD4 inhibition enhances cell migration by inducing EMT and autophagy in ESCC cells via the AMPK-modified pathway.Thus,the facilitating role on ESCC cell migration should be considered for BRD4 inhibitor clinical application to ESCC patients.展开更多
SWI/SNF chromatin remodelers are evolutionarily conserved multiprotein complexes that use the energy of ATP hydrolysis to change chromatin structure.A characteristic feature of SWI/SNF remodelers is the occurrence in ...SWI/SNF chromatin remodelers are evolutionarily conserved multiprotein complexes that use the energy of ATP hydrolysis to change chromatin structure.A characteristic feature of SWI/SNF remodelers is the occurrence in both the catalytic ATPase subunit and some auxiliary subunits,of bromodomains,the protein motifs capable of binding acetylated histones.Here,we report that the Arabidopsis bromodomaincontaining proteins BRD1,BRD2,and BRD13 are likely true SWI/SNF subunits that interact with the core SWI/SNF components SWI3C and SWP73B.Loss of function of each single BRD protein caused early flowering but had a negligible effect on other developmental pathways.By contrast,a brd triple mutation(brdx3)led to more pronounced developmental abnormalities,indicating functional redundancy among the BRD proteins.The brdx3 phenotypes,including hypersensitivity to abscisic acid and the gibberellin biosynthesis inhibitor paclobutrazol,resembled those of swi/snf mutants.Furthermore,the BRM protein level and occupancy at the direct target loci SCL3,ABI5,and SVP were reduced in the brdx3 mutant background.Finally,a brdx3 brm-3 quadruple mutant,in which SWI/SNF complexes were devoid of all constituent bromodomains,phenocopied a loss-of-function mutation in BRM.Taken together,our results demonstrate the relevance of BRDs as SWI/SNF subunits and suggest their cooperation with the bromodomain of BRM ATPase.展开更多
Objective Our earlier research revealed a connection between microRNA-29b(miR-29b)and bromodomain-containing protein 4(BRD4)and airway inflammation in chronic obstructive pulmonary disease(COPD).We examined their corr...Objective Our earlier research revealed a connection between microRNA-29b(miR-29b)and bromodomain-containing protein 4(BRD4)and airway inflammation in chronic obstructive pulmonary disease(COPD).We examined their correlation with airway inflammation and dysbiosis in COPD individuals who had ceased smoking.Methods Bacterial community composition and diversity were evaluated in bronchoalveolar lavage fluid(BALF)from COPD patients who had ceased smoking,and the expression of miR-29b/BRD4,interleukin(IL)-6 and IL-8 in bronchial brushings was measured.BEAS-2B cells were exposed to COPD BALF filtrate to establish an in vitro model.The expression levels of miR-29b,BRD4,IL-6,and IL-8 were subsequently assessed in these treated cells.Results The bacterial community composition in the lungs of individuals with COPD was different from that in the lungs of non-COPD subjects.In COPD patients,lung microbial diversity was significantly reduced,and this decline was correlated with both pulmonary function and airway inflammation.Additionally,the expression of miR-29b was lowered,whereas BRD4 expression was elevated in the lower airways of individuals with COPD.Both miR-29b and BRD4 were linked with pulmonary function,airway inflammation,and diversity indices.miR-29b regulated the production of inflammatory cytokines induced by BALF filtrate through its targeting of BRD4 in bronchial epithelial cells.Conclusion Our findings indicate that airway inflammation is associated with airway dysbiosis in COPD patients after smoking cessation and that miR-29b/BRD4 are involved in dysbiosis-associated airway inflammation.展开更多
Objective:To study the correlation of bromodomain-containing protein 4(BRD4)and S-phase kinase-associated protein 2(Skp2)expression levels in ultrasound-guided thyroid nodule fine needle aspiration biopsy tissue with ...Objective:To study the correlation of bromodomain-containing protein 4(BRD4)and S-phase kinase-associated protein 2(Skp2)expression levels in ultrasound-guided thyroid nodule fine needle aspiration biopsy tissue with the pathological features of nodules.Methods:The tissues obtained in ultrasound-guided thyroid nodule fine needle aspiration biopsy in our hospital between March 2015 and March 2018 was selected and divided into malignant group and benign group according to the pathological results,and the expression levels of BRD4,Skp2,proliferation genes and angiogenesis genes were detected.Results:The BRD4 and Skp2 mRNA expression in thyroid nodules of the malignant group were significantly higher than those of the benign group,and the BRD4 and Skp2 mRNA expression in the malignant group of thyroid nodules with TNM III-IV,capsular invasion and lymph node metastasis were significantly higher than those in the thyroid nodules with TNM I-II,without capsular invasion and without lymph node metastasis;cyclin D1(CCND1),β-catenin,proliferation cell nuclear antigen(PCNA),vascular endothelial growth factor(VEGF),endothelial cell specific molecule-1(ESM-1),Survivin and cyclooxygenase 2(COX2)mRNA expression in thyroid nodules of the malignant group were obviously higher than those of the benign group and positively correlated with BRD4 and Skp2 while cyclin G2(CCNG2)and endostatin(ES)mRNA expression were significantly lower than those of the benign group and negatively correlated with BRD4 and Skp2.Conclusion:The high expression of BRD4 and Skp2 in malignant thyroid nodules is correlated with the pathological changes and can change the expression of proliferation genes and angiogenesis genes.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
文摘Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
基金supported by the National Natural Science Foundation of China(32200399 to Y.W.,32125006 to S.G.)Natural Science Foundation of Shandong Province(ZR2024ZD40 to S.G.,ZR2024MC112 to Y.W.)+4 种基金Young Talent of Lifting Engineering for Science and Technology in Shandong,China(SDAST2024QTA008 to Y.W.)Fundamental Research Funds for the Central Universities(202441014 to Y.W.)Postdoctoral Fellowship Program of the China Postdoctoral Science Foundation(CPSF)(GZC20232503 to Y.L.)China Postdoctoral Science Foundation(2024M753050 to Y.L.)Laoshan Laboratory(LSKJ202203203 to S.G.)。
文摘Bromodomain(BRD)-containing proteins are central mediators of gene regulation,serving as key components of chromatin remodeling complexes and histone recognition scaffolds.By specifically recognizing acetylated lysine residues on histones(Kac)via their conserved BRD,these proteins influence chromatin structure and gene expression.Although their overarching role is well-established,the precise molecular functions and mechanisms of individual BRD proteins remain incompletely characterized.The ciliate Tetrahymena thermophila,a unicellular eukaryote with a transcriptionally active macronucleus enriched in histone acetylation,is an excellent model for exploring the significance of BRD-containing proteins.In this comprehensive review,all BRD-containing proteins encoded in the T.thermophila genome are systematically examined,including their expression profiles,histone acetylation targets,interacting proteins,and potential roles.This review lays the groundwork for future investigations into the complex roles of BRD proteins in chromatin remodeling and transcription regulation,offering insights into basic eukaryotic biology and the molecular mechanisms underlying BRD-linked diseases.
基金supported by National Natural Science Foundation of China(81473091,81673290 and U1603123)
文摘OBJECTIVE To discover a small-molecule bromodomain-containing protein 4(BRD4)inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer and exploreits potential mechanisms.METHODS BRD4 interactors were analyzed by PPI network prediction and The Cancer Genome Atlas(TCGA)analysis.The interaction between BRD4 and AMPK was confirmed by co-immunoprecipitation assay.Novel BRD4 inhibitors were designed and synthesized based upon pharmacophore analysis of BRD4(1),then screened by antiproliferative activity and Alpha Screen of BRD4(1).The selectivity of the best candidate compound 8f was validated by co-crystallization,FRET assay and co-immuno precipitation assay.The mechanisms of 8f were investigated by fluorescence microscopy,electron microscopy,Western blotting,immunocytochemistry,si RNA and GFP-m RFP-LC3 plasmid transfections,as well as immunohistochemistry and immunofluorescence.Potential mechanisms were discovered by i TRAQ-based proteomics analysis and the therapeutic effect of 8f was assessed by xenograft breast cancer mouse and zebrafish models.RESULTS We identified that BRD4 interacted with AMPK,which was remarkably downregulated in breast cancer.We next designed and synthesized 49 candidate compounds,and eventually discovered a selective small-molecule inhibitor of BRD4(8f).Subsequently,8f was discovered to induce autophagyassociated cell death(ACD)by BRD4-AMPK interaction,and thus activating AMPK-m TOR-ULK1-modulated autophagic pathway in breast cancer cells.Interestingly,the i TRAQ-based proteomics analyses revealed that 8f induced ACD pathways,involved in HMGB1,VDAC1/2 and e EF2.Moreover,8f displayed a therapeutic potential on both xenograft breast cancer mouse and zebrafish models.CONCLUSION We discovered a novel small-molecule inhibitor of BRD4 that induces BRD4-AMPK-modulated ACD in breast cancer,which may provide a candidate drug for future cancer therapy.
基金the Key Project of Science and Technology of Xinxiang,No.GG2020027the Health Commission of Henan Province of China,No.SBGJ202102188.
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC),the predominant type of esophageal cancer,has a 5-year survival rate less than 20%.Although the cause of poor prognosis is the high incidence and mortality of ESCC,the high rate of metastasis after esophageal cancer surgery is the main cause of death after the surgery.Bromodomain-containing protein 4(BRD4),an epigenetic reader of chromatinacetylated histones in tumorigenesis and development,plays an essential role in regulating oncogene expression.BRD4 inhibition and BRD4 inhibition-based treatment can potentially suppress ESCC growth.However,the effects and mechanisms of action of BRD4 on ESCC cell migration remain unclear.AIM To explore the effect of BRD4 on cell migration of ESCC in vitro and its possible molecular mechanism.METHODS Human ESCC cell lines KYSE-450 and KYSE-150 were used.The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay was performed to examine cell proliferation,and the transwell migration assay was conducted to test ESCC cell migration.JQ1,a BRD4 inhibitor,was applied to cells,and BRD4 siRNA was transfected into ESCC cells to knockdown endogenous BRD4.GFP-RFP-LC3 adenovirus was infected into ESCC cells to evaluate the effect of JQ1 on autophagy.Western blotting was performed to determine the protein levels of BRD4,E-cadherin,vimentin,AMP-activated protein kinase(AMPK),and p-AMPK.RESULTS BRD4 was either downregulated by small interfering RNA or pretreated with JQ1 in ESCC cells,leading to increased tumor migration in ESCC cells in a dose-and time-dependent manner.Inhibition of BRD4 not only significantly suppressed cell proliferation but also strongly increased cell migration by inducing epithelial-mesenchymal transition(EMT).The protein expression of vimentin was increased and E-cadherin decreased in a dose-dependent manner,subsequently promoting autophagy in KYSE-450 and KYSE-150 cells.Pretreatment with JQ1,a BRD4 inhibitor,inhibited BRD4-induced LC3-II activation and upregulated AMPK phosphorylation in a dosedependent manner.Additionally,an increased number of autophagosomes and autolysosomes were observed in JQ1-treated ESCC cells.The autophagy inhibitor 3-methyladenine(3-MA)reversed the effects of BRD4 knockdown on ESCC cell migration and blocked JQ1-induced cell migration.3-MA also downregulated the expression of vimentin and upregulation E-cadherin.CONCLUSION BRD4 inhibition enhances cell migration by inducing EMT and autophagy in ESCC cells via the AMPK-modified pathway.Thus,the facilitating role on ESCC cell migration should be considered for BRD4 inhibitor clinical application to ESCC patients.
基金supported by grants from National Science Centre project nos.2014/15/N/NZ2/00396 to K.J.,2014/13/B/NZ1/00967 to A.J.,and 2017/26/E/NZ2/00899 to R.A.sponsored in part by the Center for Preclinical Research and Technology(CePT)+1 种基金a project co-sponsored by the European Regional Development Fund and Innovative EconomyThe National Cohesion Strategy of Poland.
文摘SWI/SNF chromatin remodelers are evolutionarily conserved multiprotein complexes that use the energy of ATP hydrolysis to change chromatin structure.A characteristic feature of SWI/SNF remodelers is the occurrence in both the catalytic ATPase subunit and some auxiliary subunits,of bromodomains,the protein motifs capable of binding acetylated histones.Here,we report that the Arabidopsis bromodomaincontaining proteins BRD1,BRD2,and BRD13 are likely true SWI/SNF subunits that interact with the core SWI/SNF components SWI3C and SWP73B.Loss of function of each single BRD protein caused early flowering but had a negligible effect on other developmental pathways.By contrast,a brd triple mutation(brdx3)led to more pronounced developmental abnormalities,indicating functional redundancy among the BRD proteins.The brdx3 phenotypes,including hypersensitivity to abscisic acid and the gibberellin biosynthesis inhibitor paclobutrazol,resembled those of swi/snf mutants.Furthermore,the BRM protein level and occupancy at the direct target loci SCL3,ABI5,and SVP were reduced in the brdx3 mutant background.Finally,a brdx3 brm-3 quadruple mutant,in which SWI/SNF complexes were devoid of all constituent bromodomains,phenocopied a loss-of-function mutation in BRM.Taken together,our results demonstrate the relevance of BRDs as SWI/SNF subunits and suggest their cooperation with the bromodomain of BRM ATPase.
基金supported by a grant from the COPD Research Programs of Beijing Bethune Charitable Foundation(No.BJ-RW2020015J).
文摘Objective Our earlier research revealed a connection between microRNA-29b(miR-29b)and bromodomain-containing protein 4(BRD4)and airway inflammation in chronic obstructive pulmonary disease(COPD).We examined their correlation with airway inflammation and dysbiosis in COPD individuals who had ceased smoking.Methods Bacterial community composition and diversity were evaluated in bronchoalveolar lavage fluid(BALF)from COPD patients who had ceased smoking,and the expression of miR-29b/BRD4,interleukin(IL)-6 and IL-8 in bronchial brushings was measured.BEAS-2B cells were exposed to COPD BALF filtrate to establish an in vitro model.The expression levels of miR-29b,BRD4,IL-6,and IL-8 were subsequently assessed in these treated cells.Results The bacterial community composition in the lungs of individuals with COPD was different from that in the lungs of non-COPD subjects.In COPD patients,lung microbial diversity was significantly reduced,and this decline was correlated with both pulmonary function and airway inflammation.Additionally,the expression of miR-29b was lowered,whereas BRD4 expression was elevated in the lower airways of individuals with COPD.Both miR-29b and BRD4 were linked with pulmonary function,airway inflammation,and diversity indices.miR-29b regulated the production of inflammatory cytokines induced by BALF filtrate through its targeting of BRD4 in bronchial epithelial cells.Conclusion Our findings indicate that airway inflammation is associated with airway dysbiosis in COPD patients after smoking cessation and that miR-29b/BRD4 are involved in dysbiosis-associated airway inflammation.
基金Hubei Provincial Natural Science Foundation Project.Project No:WJ2015MB125.
文摘Objective:To study the correlation of bromodomain-containing protein 4(BRD4)and S-phase kinase-associated protein 2(Skp2)expression levels in ultrasound-guided thyroid nodule fine needle aspiration biopsy tissue with the pathological features of nodules.Methods:The tissues obtained in ultrasound-guided thyroid nodule fine needle aspiration biopsy in our hospital between March 2015 and March 2018 was selected and divided into malignant group and benign group according to the pathological results,and the expression levels of BRD4,Skp2,proliferation genes and angiogenesis genes were detected.Results:The BRD4 and Skp2 mRNA expression in thyroid nodules of the malignant group were significantly higher than those of the benign group,and the BRD4 and Skp2 mRNA expression in the malignant group of thyroid nodules with TNM III-IV,capsular invasion and lymph node metastasis were significantly higher than those in the thyroid nodules with TNM I-II,without capsular invasion and without lymph node metastasis;cyclin D1(CCND1),β-catenin,proliferation cell nuclear antigen(PCNA),vascular endothelial growth factor(VEGF),endothelial cell specific molecule-1(ESM-1),Survivin and cyclooxygenase 2(COX2)mRNA expression in thyroid nodules of the malignant group were obviously higher than those of the benign group and positively correlated with BRD4 and Skp2 while cyclin G2(CCNG2)and endostatin(ES)mRNA expression were significantly lower than those of the benign group and negatively correlated with BRD4 and Skp2.Conclusion:The high expression of BRD4 and Skp2 in malignant thyroid nodules is correlated with the pathological changes and can change the expression of proliferation genes and angiogenesis genes.
