Besser REJ,Knight BA,Shepherd MH等的"Urinary C-peptide creatinine ratio(UCPCR)is a practical outpatient tool for identifying HNF1A/HNF4A MODY from long duration type 1diabetes"(Diabetes Care,2011,34:286-291...Besser REJ,Knight BA,Shepherd MH等的"Urinary C-peptide creatinine ratio(UCPCR)is a practical outpatient tool for identifying HNF1A/HNF4A MODY from long duration type 1diabetes"(Diabetes Care,2011,34:286-291)一文比较了成人中HNF1A/4A MODY、T1DM、T2DM中的UCPCR水平,证实了UCPCR是可用于鉴别HNF1α/HNF4αMODY与长期T1DM的非侵入性门诊诊断工具。并指出对于从病程>5年的T1DM和MODY的鉴别,UCPCR可用于确定是否需要基因检测。展开更多
胃癌的发生是由正常胃黏膜经历慢性萎缩性胃炎、肠化生、异型增生直至胃癌发生的多阶段渐进性过程。其中肠化生是胃癌尤其是肠型胃癌重要的癌前病变。有研究证实,在肠化生及胃癌的发生过程中,性别决定区Y框蛋白2(SRY related HMG box-2,...胃癌的发生是由正常胃黏膜经历慢性萎缩性胃炎、肠化生、异型增生直至胃癌发生的多阶段渐进性过程。其中肠化生是胃癌尤其是肠型胃癌重要的癌前病变。有研究证实,在肠化生及胃癌的发生过程中,性别决定区Y框蛋白2(SRY related HMG box-2,SOX2)、尾侧型同源转录因子2(caudal related homeobox transcription factor-2,CDX2)和肝细胞核因子(hepatocyte nuclear factor,HNF)4α均有参与,而且3个分子间存在明显相关性。因此,本文对目前SOX2、CDX2和HNF4α与胃癌的相关研究进展作一综述。展开更多
Objective:Hepatocyte nuclear factor 4α(HNF4 A)has been demonstrated to be an oncogene in gastric cancer(GC).However,the roles of different HNF4 A isoforms derived from the 2 different promoters(P1 and P2)and the unde...Objective:Hepatocyte nuclear factor 4α(HNF4 A)has been demonstrated to be an oncogene in gastric cancer(GC).However,the roles of different HNF4 A isoforms derived from the 2 different promoters(P1 and P2)and the underlying mechanisms remain obscure.Methods:The expression and prognostic values of P1-and P2-HNF4 A were evaluated in The Cancer Genome Atlas(TCGA)databases and GC tissues.Then,functional assays of P1-and P2-HNF4 A were conducted both in vivo and in vitro.High-throughput RNA-seq was employed to profile downstream pathways in P1-and P2-HNF4 A-overexpressing GC cells.The expression and gene regulation network of the candidate target genes identified by RNA-seq were characterized based on data mining and functional assays.Results:HNF4 A amplification was a key characteristic of GC in TCGA databases,especially for the intestinal type and early stage.Moreover,P1-HNF4 A expression was significantly higher in tumor tissues than in adjacent non-tumor tissues(P<0.05),but no significant differences were found in P2-HNF4 A expression(P>0.05).High P1-HNF4 A expression indicated poor prognoses in GC patients(P<0.01).Furthermore,P1-HNF4 A overexpression significantly promoted SGC7901 and BGC823 cell proliferation,invasion and migration in vitro(P<0.01).Murine xenograft experiments showed that P1-HNF4 A overexpression promoted tumor growth(P<0.05).Mechanistically,RNA-seq showed that the cytokine-cytokine receptor interactions pathway was mostly enriched in P1-HNF4 A-overexpressing GC cells.Finally,chemokine(C-C motif)ligand 15 was identified as a direct target of P1-HNF4 A in GC tissues.Conclusions:P1-HNF4 A was the main oncogene during GC progression.The cytokine-cytokine receptor interaction pathway played a pivotal role and may be a promising therapeutic target.展开更多
文摘Besser REJ,Knight BA,Shepherd MH等的"Urinary C-peptide creatinine ratio(UCPCR)is a practical outpatient tool for identifying HNF1A/HNF4A MODY from long duration type 1diabetes"(Diabetes Care,2011,34:286-291)一文比较了成人中HNF1A/4A MODY、T1DM、T2DM中的UCPCR水平,证实了UCPCR是可用于鉴别HNF1α/HNF4αMODY与长期T1DM的非侵入性门诊诊断工具。并指出对于从病程>5年的T1DM和MODY的鉴别,UCPCR可用于确定是否需要基因检测。
文摘胃癌的发生是由正常胃黏膜经历慢性萎缩性胃炎、肠化生、异型增生直至胃癌发生的多阶段渐进性过程。其中肠化生是胃癌尤其是肠型胃癌重要的癌前病变。有研究证实,在肠化生及胃癌的发生过程中,性别决定区Y框蛋白2(SRY related HMG box-2,SOX2)、尾侧型同源转录因子2(caudal related homeobox transcription factor-2,CDX2)和肝细胞核因子(hepatocyte nuclear factor,HNF)4α均有参与,而且3个分子间存在明显相关性。因此,本文对目前SOX2、CDX2和HNF4α与胃癌的相关研究进展作一综述。
基金supported by the National Natural Science Foundation of China(Grant No.81873554)Shaanxi Foundation for Innovation Team of Science and Technology(Grant No.2018TD-003)。
文摘Objective:Hepatocyte nuclear factor 4α(HNF4 A)has been demonstrated to be an oncogene in gastric cancer(GC).However,the roles of different HNF4 A isoforms derived from the 2 different promoters(P1 and P2)and the underlying mechanisms remain obscure.Methods:The expression and prognostic values of P1-and P2-HNF4 A were evaluated in The Cancer Genome Atlas(TCGA)databases and GC tissues.Then,functional assays of P1-and P2-HNF4 A were conducted both in vivo and in vitro.High-throughput RNA-seq was employed to profile downstream pathways in P1-and P2-HNF4 A-overexpressing GC cells.The expression and gene regulation network of the candidate target genes identified by RNA-seq were characterized based on data mining and functional assays.Results:HNF4 A amplification was a key characteristic of GC in TCGA databases,especially for the intestinal type and early stage.Moreover,P1-HNF4 A expression was significantly higher in tumor tissues than in adjacent non-tumor tissues(P<0.05),but no significant differences were found in P2-HNF4 A expression(P>0.05).High P1-HNF4 A expression indicated poor prognoses in GC patients(P<0.01).Furthermore,P1-HNF4 A overexpression significantly promoted SGC7901 and BGC823 cell proliferation,invasion and migration in vitro(P<0.01).Murine xenograft experiments showed that P1-HNF4 A overexpression promoted tumor growth(P<0.05).Mechanistically,RNA-seq showed that the cytokine-cytokine receptor interactions pathway was mostly enriched in P1-HNF4 A-overexpressing GC cells.Finally,chemokine(C-C motif)ligand 15 was identified as a direct target of P1-HNF4 A in GC tissues.Conclusions:P1-HNF4 A was the main oncogene during GC progression.The cytokine-cytokine receptor interaction pathway played a pivotal role and may be a promising therapeutic target.
