CITED2(CBP/p300-interacting transactivator with Glu/Asp-rich C-terminal domain,2)is a ubiquitously expressed protein exhibiting a high affinity for the CH1 domain of the transcriptional co-activators CBP/p300,for whic...CITED2(CBP/p300-interacting transactivator with Glu/Asp-rich C-terminal domain,2)is a ubiquitously expressed protein exhibiting a high affinity for the CH1 domain of the transcriptional co-activators CBP/p300,for which it competes with hypoxia-inducible factors(HIFs).CITED2 is particularly efficient in the inhibition of HIF-1α-dependent transcription in different contexts,ranging from organ development and metabolic homeostasis to tissue regeneration and immunity,being also potentially involved in various other physiological processes.In addition,CITED2 plays an important role in inhibiting HIF in some diseases,including kidney and heart diseases and type 2-diabetes.In the particular case of cancer,CITED2 either functions by promoting or suppressing cancer development depending on the context and type of tumors.For instance,CITED2 overexpression promotes breast and prostate cancers,as well as acute myeloid leukemia,while its expression is downregulated to sustain colorectal cancer and hepatocellular carcinoma.In addition,the role of CITED2 in the maintenance of cancer stem cells reveals its potential as a target in non-small cell lung carcinoma and acute myeloid leukemia,for example.But besides the wide body of evidence linking both CITED2 and HIF signaling to carcinogenesis,little data is available regarding CITED2 role as a negative regulator of HIF-1αspecifically in cancer.Therefore,comprehensive studies exploring further the interactions of these two important mediators in cancer-specific models are sorely needed and this can potentially lead to the development of novel targeted therapies.展开更多
目的用外显子捕获-高通量测序(exon-capture high-throughput sequencing,EC-HTS)技术寻找法洛四联症(tetralogy of fallot,TOF)胎儿可能存在的遗传学致病性证据,并探讨其在产前分子遗传学诊断中的价值。方法选择经超声心动图发现且G显...目的用外显子捕获-高通量测序(exon-capture high-throughput sequencing,EC-HTS)技术寻找法洛四联症(tetralogy of fallot,TOF)胎儿可能存在的遗传学致病性证据,并探讨其在产前分子遗传学诊断中的价值。方法选择经超声心动图发现且G显带和微阵列比较基因组杂交(array-based comparative genomic hybridization,a CGH)分析结果均正常的9例TOF胎儿作为研究对象,以63个人类已知的先天性心脏病致病基因作为检测靶点制作捕获芯片,用EC-HTS技术进行检测,数据经过Calling、数据库比对、软件分析得到最终病理性突变位点;并用Sanger测序对其进行验证。结果在9例胎儿中共检测到单核苷酸多态性(SNP)位点732个,结果经过生物信息学分析得到致病性突变位点3个:CITED2 c.574_579 del AGCGGC(p.S192_G193del纯合突变,CHD7c.2550_2554 del GAGAA(p.K850Nfs*6)杂合突变,NOTCH2 c.4918T>C(p.F1640L)杂合突变。Sanger测序结果验证了这3个突变位点的真实存在,父母溯源检测发现这3个点突变均为新发突变。结论用靶向性EC-HTS技术发现了3例TOF胎儿存在病理性基因突变,可能为其致病的遗传学病因。展开更多
文摘目的:探讨多囊卵巢综合征(polycystic ovary syndrome,PCOS)与CITED2基因表达变化的相关性。方法:收集新疆维吾尔自治区人民医院北院2014年5月至2016年12月收治的PCOS患者114例,另取新疆维吾尔自治区人民医院北院正常月经周期的健康育龄期女性80例作为对照组。使用电化学发光法测定卵泡刺激素(follicle-stimulating hormone,FSH)、黄体生成素(luteotropic hormone,LH)、睾酮(testosterone,T)及雌二醇(estradiol,E2)水平。稳态模型测定胰岛素分泌指数(homeostasis model assessmentβ,HOMA-β)和胰岛素抵抗指数(homeostasis model assessment-insulin resistance,HOMA-IR)。荧光定量PCR检测CITED2基因表达。结果:PCOS患者CITED2基因的2^(-△Ct)值为0.146±0.032,对照组为0.097±0.022,两组间差异具有统计学意义(t=3.135,P=0.032)。CITED2基因表达与PCOS患者FSH呈负相关(r=-0.216,P=0.041),与LH(r=0.382,P=0.022),T(r=0.394,P=0.016),E2(r=0.375,P=0.026),HOMA-β(r=0.351,P=0.031)和HOMA-IR(r=0.326,P=0.033)呈正相关。结论:PCOS患者CITED2基因高表达,这可能是PCOS患者性激素紊乱和胰岛素抵抗的主要影响因素。
文摘CITED2(CBP/p300-interacting transactivator with Glu/Asp-rich C-terminal domain,2)is a ubiquitously expressed protein exhibiting a high affinity for the CH1 domain of the transcriptional co-activators CBP/p300,for which it competes with hypoxia-inducible factors(HIFs).CITED2 is particularly efficient in the inhibition of HIF-1α-dependent transcription in different contexts,ranging from organ development and metabolic homeostasis to tissue regeneration and immunity,being also potentially involved in various other physiological processes.In addition,CITED2 plays an important role in inhibiting HIF in some diseases,including kidney and heart diseases and type 2-diabetes.In the particular case of cancer,CITED2 either functions by promoting or suppressing cancer development depending on the context and type of tumors.For instance,CITED2 overexpression promotes breast and prostate cancers,as well as acute myeloid leukemia,while its expression is downregulated to sustain colorectal cancer and hepatocellular carcinoma.In addition,the role of CITED2 in the maintenance of cancer stem cells reveals its potential as a target in non-small cell lung carcinoma and acute myeloid leukemia,for example.But besides the wide body of evidence linking both CITED2 and HIF signaling to carcinogenesis,little data is available regarding CITED2 role as a negative regulator of HIF-1αspecifically in cancer.Therefore,comprehensive studies exploring further the interactions of these two important mediators in cancer-specific models are sorely needed and this can potentially lead to the development of novel targeted therapies.
文摘目的用外显子捕获-高通量测序(exon-capture high-throughput sequencing,EC-HTS)技术寻找法洛四联症(tetralogy of fallot,TOF)胎儿可能存在的遗传学致病性证据,并探讨其在产前分子遗传学诊断中的价值。方法选择经超声心动图发现且G显带和微阵列比较基因组杂交(array-based comparative genomic hybridization,a CGH)分析结果均正常的9例TOF胎儿作为研究对象,以63个人类已知的先天性心脏病致病基因作为检测靶点制作捕获芯片,用EC-HTS技术进行检测,数据经过Calling、数据库比对、软件分析得到最终病理性突变位点;并用Sanger测序对其进行验证。结果在9例胎儿中共检测到单核苷酸多态性(SNP)位点732个,结果经过生物信息学分析得到致病性突变位点3个:CITED2 c.574_579 del AGCGGC(p.S192_G193del纯合突变,CHD7c.2550_2554 del GAGAA(p.K850Nfs*6)杂合突变,NOTCH2 c.4918T>C(p.F1640L)杂合突变。Sanger测序结果验证了这3个突变位点的真实存在,父母溯源检测发现这3个点突变均为新发突变。结论用靶向性EC-HTS技术发现了3例TOF胎儿存在病理性基因突变,可能为其致病的遗传学病因。
