【摘 要】
：
Previous studies have established the link between aberrant microRNA(miRNA)level and hypoxia in various neoplasms.However,how these aberrant miRNAs induced by hypoxia modulate tumor progression is sti
【机 构】
：
第二军医大学基础医学部医学遗传学教研室,上海,200433
【出 处】
：
中华医学会2012年医学遗传学年会暨全国第十一次医学遗传学学术会议
论文部分内容阅读
Previous studies have established the link between aberrant microRNA(miRNA)level and hypoxia in various neoplasms.However,how these aberrant miRNAs induced by hypoxia modulate tumor progression is still unclear.In this study,the miRNA patterns of colorectal carcinoma(CRC)cells in hypoxia were screened by a high-resolution miRNA microarray and the hypoxia-induced repression of miR-15-16 was confirmed.This repression was associated with higher tumor stage and poor prognosis in CRC.It was further disclosed that the hypoxia-induced repression of miR-15-16 promoted angiogenesis and metastasis by the loss of post-transcriptional inhibition of fibroblast growth factor-2(FGF2),Moreover,the promoter of the host gene (deleted in lymphocytic leukemia 2,DLEU2)of the miR-15-16 cluster was mapped and three Myc/Max binding sites responding in hypoxia were identified.Then,the transcriptional repression of c-Myc to miR-15-16 via these Myc/Max binding sites in hypoxia was validated.Finally,we verified that the functional "c-Myc/miR-15-16/FGF2"pathway would play an important role in hypoxia-induced distant tumor metastasis.In a word,c-Myc-mediated repression of the miR-15-16 cluster in hypoxia promotes tumor angiogenesis and distant metastasis by upregulating FGF2.Our study provides a better understanding of the coping mechanisms of microRNAs in response to hypoxia and may be helpful in developing more effective prognostic markers or treatment targets for solid tumors.
其他文献
In this report,we identified a homozygous missense mutation in a novel gene,TMEM132E (transmembrane protein 132E),in a chinese consanguineous family with nonsyndromic hearing loss using whole exome se
BACKGROUND Hypertensive disorders complicating pregnancy(HDCP)is one of the most common complication in obstetric.The real pathogenesis about HDCP is still unknown.Research had shown that the genesis
目的 探讨骨髓间充质干细胞(mesenchymal stem cells,MSCs)在体外模拟的肿瘤微环境中是否受到其中过度表达的致瘤性酪氨酸激酶信号分子的影响而发生恶性转化,为安全有效地利用MSCs提供一定的前期理论基础和实验依据.方法 本实验分筛选实验和验证实验两部分,筛选实验部分设为实验组,对照组和空白对照组三组.实验组为C6胶质瘤与MSCs间接共培养模拟肿瘤微环境下MSCs的生长；对照组为
目的 研究囊性纤维化转倒调节因子(cystic fibrosis transmembrane conductance regulator,CFTR)第8内含子中的5T等位基因多态性与中国汉族男性先天性输精管缺如(congenital bilateral absence of vas deferens,CBAVD)的相关性.方法 选择33例男性先天性双侧输精管缺如患者和99例对照普通无精症患者.提取
目的 食管鳞状细胞癌是我国十大恶性肿瘤之一,尤以男性高发.近年来,虽然临床对食管癌的诊治水平取得了显著进展,但是中晚期患者手术总体5年生存率仍然徘徊在10％左右.运用分子生物学技术检测基因及蛋白的改变,寻找灵敏度高、特异性强的分子标志物,被认为是改善食管癌诊断和治疗最有前景的手段之一.本研究旨在检测TIMP1蛋白在食管鳞癌中的表达情况,并探讨其在临床诊断与预后判断的应用价值.方法 应用组织微阵列联
High myopia,highly prevalent in the Chinese population,is a leading cause of visual impairment worldwide.Genetic factors play a critical role in the development of this visual disorder.Genome-wide ass
目的 阴道正常菌群对于维持阴道微生态环境的平衡起着十分重要的作用.以往采用的培养方法由于其本身技术的局限,无法获得相对准确的细菌谱的分布.本研究采用微生物组学方法,对中国健康育龄期汉族妇女阴道菌群的结构及其系统进化特征进行了初步研究,为进一步筛选和开发适合我国妇女生殖道健康的益生菌提供依据.方法 直接从阴道分泌物拭子中抽提细菌基因组DNA,采用细菌通用引物27f和1492r扩增16S rRNA基因
Background Massively parallel sequencing of DNA molecules in the plasma of pregnant women has been shown to allow noninvasive prenatal detection of fetal trisomy 21,18and13,could be a potential useful
Epithelial-Mesenchymal Transition(EMT)plays a pivotal role in tumor invasion and dissemination.Although it is well documented that EMT occurred predominantly at the tumor edge where it is induced by c
Liver regeneration driven by hepatocyte proliferation is necessary for tissue repair and survival after acute liver injury,liver transplantation,and chronic hepatic disease.After a partial hepatectomy