BACKGROUND Kabuki syndrome(KS)is a rare syndrome characterized by multisystem congenital anomalies and developmental disorder.KMT2D and KDM6A mutations were identified as the main causative genes in KS patients.There ...BACKGROUND Kabuki syndrome(KS)is a rare syndrome characterized by multisystem congenital anomalies and developmental disorder.KMT2D and KDM6A mutations were identified as the main causative genes in KS patients.There are few case reports and genetic analyses,especially of KDM6A gene mutation,in China.CASE SUMMARY This study reports a de novo KDM6A mutation in a Chinese infant with KS.A 2-month-old Chinese baby was diagnosed with KS,which manifested as hypoglycemia,congenital anal atresia at birth,feeding difficulties,hypotonia,and serious postnatal growth retardation.He died of recurrent respiratory infections at age 13 mo.DNA sequencing of his blood DNA revealed a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19).CONCLUSION We present a Chinese KS patient with a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19),broadening the mutation spectrum.展开更多
赖氨酸特异性去甲基化酶6B(lysine-specific demethylase 6B,KDM6B)是含Jumonji C结构域蛋白家族(Jumonji C domain-containing protein family,JmjC)中的一种重要表观遗传因子,不仅在细胞分化、炎症反应、组织稳态和神经性疾病中发挥...赖氨酸特异性去甲基化酶6B(lysine-specific demethylase 6B,KDM6B)是含Jumonji C结构域蛋白家族(Jumonji C domain-containing protein family,JmjC)中的一种重要表观遗传因子,不仅在细胞分化、炎症反应、组织稳态和神经性疾病中发挥表观遗传调控作用,还对巨噬细胞的功能、免疫反应等具有关键调控意义。作为JmjC家族中唯一能响应类Toll受体(Toll-like receptor,TLR)信号的成员,KDM6B可在TLR信号刺激下被激活从而发挥功能。研究发现,KDM6B可以通过调节巨噬细胞的极化、影响细胞因子的表达水平以及参与肿瘤微环境调控等方式影响巨噬细胞,因此,KDM6B在免疫反应、炎症反应以及肿瘤等病理生理过程中发挥重要作用。KDM6B作为关键的表观遗传因子对巨噬细胞的功能具有调控作用,包括调节巨噬细胞的极化、炎症反应以及促纤维化等,有望成为研究免疫、炎症及肿瘤等相关疾病的潜在靶点。展开更多
目的探讨KDM6A突变或表达与胃癌临床病理特征的关系及其对胃癌患者预后的影响。方法通过二代测序对57例胃癌组织进行全外显子测序,以及Cbioportal、Kaplan Meier-Plotter和the Human Protein Atlas等生物信息数据库资料,分析KDM6A突变...目的探讨KDM6A突变或表达与胃癌临床病理特征的关系及其对胃癌患者预后的影响。方法通过二代测序对57例胃癌组织进行全外显子测序,以及Cbioportal、Kaplan Meier-Plotter和the Human Protein Atlas等生物信息数据库资料,分析KDM6A突变与胃癌临床病理特征和胃癌患者总生存时间的关系。结果57例胃癌样本中,KDM6A突变14例,突变率为24.6%。突变组与未突变组比较,Borrmann分型、T分期、TNM分期和肿瘤直径差异有统计学意义(均P<0.05),突变组患者的中位生存时间(53.5个月)短于未突变组(72.0个月,P=0.007)。Kaplan Meier-Plotter数据库的875例胃癌患者中,KDM6A低表达者655例,高表达者220例,低表达患者的中位生存时间(23.5个月)短于高表达患者(30.8个月,P=0.002)。在男性、Ⅲ期、肠型、弥漫型、单纯手术治疗和含氟尿嘧啶方案化疗的患者中,KDM6A表达与患者的总生存时间有关(均P<0.05)。Cbioportal数据库的1172例胃癌患者中,KDM6A突变者70例,未突变者1100例,突变患者的总生存时间(28.9个月)短于未突变患者(35.9个月,P<0.001)。the Human Protein Atlas数据库的355例胃癌患者中,KDM6A高表达97例,KDM6A低表达258例,低表达患者的中位生存时间(13.7个月)短于高表达患者(19.8个月,P=0.022)。结论KDM6A突变、低表达胃癌患者的生存时间更短,且与临床病理因素相关,有可能成为胃癌诊断及治疗的潜在靶点。展开更多
Background:Bladder cancer is a highly prevalent and lethal malignant tumor characterized by frequent mutations/deletions of lysine-specific demethylase 6A(KDM6A),which is suggested to be a key event in cancer progress...Background:Bladder cancer is a highly prevalent and lethal malignant tumor characterized by frequent mutations/deletions of lysine-specific demethylase 6A(KDM6A),which is suggested to be a key event in cancer progression and metastasis.Beta-elemene has been shown to inhibit metastasis and growth of various tumors,but its effect on KDM6A-null bladder cancer cells remains unknown.Objective:This study aimed to investigate the potential and molecular mechanism ofβ-elemene in inhibiting the growth of KDM6A-null bladder cancer.Methods:This study examined the migration ability and viability of RT-4(KDM6A wild-type)and KU19-19(KDM6A-null)cell lines using wound healing assay and CCK-8,respectively.The inhibitory effect ofβ-elemene on KU19-19 cell migration was evaluated using transwell and immunofluorescence assays,and the expression of transfer-related proteins and genes was analyzed through western blot and qRT-PCR,respectively.Molecular docking was performed to predict the targeting ofβ-elemene,and the effects were confirmed in KDM6Aknockdown RT-4 cells.Finally,the therapeutic effect ofβ-elemene on bladder cancer was tested in animal models.Results:The study observed that loss of KDM6A increased bladder cancer cell migration,with KU19-19 exhibiting significantly stronger migration than RT-4.Further investigation revealed thatβ-elemene effectively inhibited KU19-19 cell migration,likely through targeting EZH2 as determined by molecular docking.Overexpression of KDM6A inhibited KU19-19 metastasis,while knockdown of KDM6A in RT-4 cells enhanced cell migration,which was reversed byβ-elemene treatment.Notably,in vivo testing revealed a significant suppression of KU19-19 cell growth withβ-elemene administered at a dosage of 100 mg/kg.Conclusion:β-elemene has the potential to suppress the growth of KDM6A-null bladder cancer by inhibiting epithelial-mesenchymal transition(EMT),which could make it a promising therapeutic option for patients with KDM6A-null bladder cancer.展开更多
文摘BACKGROUND Kabuki syndrome(KS)is a rare syndrome characterized by multisystem congenital anomalies and developmental disorder.KMT2D and KDM6A mutations were identified as the main causative genes in KS patients.There are few case reports and genetic analyses,especially of KDM6A gene mutation,in China.CASE SUMMARY This study reports a de novo KDM6A mutation in a Chinese infant with KS.A 2-month-old Chinese baby was diagnosed with KS,which manifested as hypoglycemia,congenital anal atresia at birth,feeding difficulties,hypotonia,and serious postnatal growth retardation.He died of recurrent respiratory infections at age 13 mo.DNA sequencing of his blood DNA revealed a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19).CONCLUSION We present a Chinese KS patient with a novel KDM6A frameshift mutation(c.704_705delAG,p.N236Sfs*26)(GRCh37/hg19),broadening the mutation spectrum.
文摘赖氨酸特异性去甲基化酶6B(lysine-specific demethylase 6B,KDM6B)是含Jumonji C结构域蛋白家族(Jumonji C domain-containing protein family,JmjC)中的一种重要表观遗传因子,不仅在细胞分化、炎症反应、组织稳态和神经性疾病中发挥表观遗传调控作用,还对巨噬细胞的功能、免疫反应等具有关键调控意义。作为JmjC家族中唯一能响应类Toll受体(Toll-like receptor,TLR)信号的成员,KDM6B可在TLR信号刺激下被激活从而发挥功能。研究发现,KDM6B可以通过调节巨噬细胞的极化、影响细胞因子的表达水平以及参与肿瘤微环境调控等方式影响巨噬细胞,因此,KDM6B在免疫反应、炎症反应以及肿瘤等病理生理过程中发挥重要作用。KDM6B作为关键的表观遗传因子对巨噬细胞的功能具有调控作用,包括调节巨噬细胞的极化、炎症反应以及促纤维化等,有望成为研究免疫、炎症及肿瘤等相关疾病的潜在靶点。
文摘目的探讨KDM6A突变或表达与胃癌临床病理特征的关系及其对胃癌患者预后的影响。方法通过二代测序对57例胃癌组织进行全外显子测序,以及Cbioportal、Kaplan Meier-Plotter和the Human Protein Atlas等生物信息数据库资料,分析KDM6A突变与胃癌临床病理特征和胃癌患者总生存时间的关系。结果57例胃癌样本中,KDM6A突变14例,突变率为24.6%。突变组与未突变组比较,Borrmann分型、T分期、TNM分期和肿瘤直径差异有统计学意义(均P<0.05),突变组患者的中位生存时间(53.5个月)短于未突变组(72.0个月,P=0.007)。Kaplan Meier-Plotter数据库的875例胃癌患者中,KDM6A低表达者655例,高表达者220例,低表达患者的中位生存时间(23.5个月)短于高表达患者(30.8个月,P=0.002)。在男性、Ⅲ期、肠型、弥漫型、单纯手术治疗和含氟尿嘧啶方案化疗的患者中,KDM6A表达与患者的总生存时间有关(均P<0.05)。Cbioportal数据库的1172例胃癌患者中,KDM6A突变者70例,未突变者1100例,突变患者的总生存时间(28.9个月)短于未突变患者(35.9个月,P<0.001)。the Human Protein Atlas数据库的355例胃癌患者中,KDM6A高表达97例,KDM6A低表达258例,低表达患者的中位生存时间(13.7个月)短于高表达患者(19.8个月,P=0.022)。结论KDM6A突变、低表达胃癌患者的生存时间更短,且与临床病理因素相关,有可能成为胃癌诊断及治疗的潜在靶点。
基金various sources,including Zhejiang Provincial Natural Science Foundation of China(grant No.LQ20H160013,LQ21H160038,and LY23H160026)the Science and Technology Development Fund,Macao SAR(File No.:0098/2021/A2).
文摘Background:Bladder cancer is a highly prevalent and lethal malignant tumor characterized by frequent mutations/deletions of lysine-specific demethylase 6A(KDM6A),which is suggested to be a key event in cancer progression and metastasis.Beta-elemene has been shown to inhibit metastasis and growth of various tumors,but its effect on KDM6A-null bladder cancer cells remains unknown.Objective:This study aimed to investigate the potential and molecular mechanism ofβ-elemene in inhibiting the growth of KDM6A-null bladder cancer.Methods:This study examined the migration ability and viability of RT-4(KDM6A wild-type)and KU19-19(KDM6A-null)cell lines using wound healing assay and CCK-8,respectively.The inhibitory effect ofβ-elemene on KU19-19 cell migration was evaluated using transwell and immunofluorescence assays,and the expression of transfer-related proteins and genes was analyzed through western blot and qRT-PCR,respectively.Molecular docking was performed to predict the targeting ofβ-elemene,and the effects were confirmed in KDM6Aknockdown RT-4 cells.Finally,the therapeutic effect ofβ-elemene on bladder cancer was tested in animal models.Results:The study observed that loss of KDM6A increased bladder cancer cell migration,with KU19-19 exhibiting significantly stronger migration than RT-4.Further investigation revealed thatβ-elemene effectively inhibited KU19-19 cell migration,likely through targeting EZH2 as determined by molecular docking.Overexpression of KDM6A inhibited KU19-19 metastasis,while knockdown of KDM6A in RT-4 cells enhanced cell migration,which was reversed byβ-elemene treatment.Notably,in vivo testing revealed a significant suppression of KU19-19 cell growth withβ-elemene administered at a dosage of 100 mg/kg.Conclusion:β-elemene has the potential to suppress the growth of KDM6A-null bladder cancer by inhibiting epithelial-mesenchymal transition(EMT),which could make it a promising therapeutic option for patients with KDM6A-null bladder cancer.
