炎性肿块肺纤维化组织中miR-21和TGFβ1的表达变化

[目的]观察炎性肿块肺纤维化组织中miR-21和转化生长因子β1(transforming growth factorβ1,TGFβ1)的表达变化,探讨两者的表达变化是否与肺纤维化形成有关.[方法]选择10例炎性肺部肿块标本,每例分别按纤维化组织和旁近正常肺组织配对留取,所有标本均采用Real-time PCR方法检测组织中miR-21和TGFβ1的表达量变化,分析其表达是否与肺纤维化有关.[结果]肺纤维化组织中miR-21和TGFβ1的表达明显高于正常旁近肺组织,且两者相比较差异均有显著性(P＜0.01).[结论]miR-21和TGFβ1在炎性肿块肺纤维化组织中高表达,其高表达与炎症导致的肺纤维化形成有关.     

循环 microRNA-21对冠心病不稳定斑块的预测意义

目的：探讨冠心病（CAD）患者循环 microRNA-21（miRNA-21）相对表达量与冠状动脉内不稳定斑块的关系。方法连续收集2012年1月至2014年12月在广州市第一人民医院心内科住院并接受冠状动脉造影（CAG）及血管内超声（IVUS）检查的 CAD 患者100例,根据 IVUS检查患者冠脉内是否具有不稳定斑块分为稳定斑块组（SP 组）45例、不稳定斑块组（UP 组）55例,并选择同期在本院体检中心进行健康体检的50例健康对照病例作为对照组。采用实时荧光定量聚合酶链式反应技术（qRT-PCR）测定入选病例空腹静脉血浆 miRNA-21的相对表达量,分析血浆 miRNA-21水平与 CAD 患者不稳定斑块的关系。结果不稳定斑块组患者血浆 miRNA-21相对表达量显著高于稳定斑块组和对照组[（0.87±0.10） vs.（0.78±0.11） vs.（0.67±0.08）,P ＜0.05],将 CAD 患者血浆 miRNA-21水平与患者是否存在不稳定斑块做出受试者工作曲线（ROC）,血浆 miRNA-21的曲线下面积（AUC）为0.869（95％CI：0.797～0.940）。多因素 Logistic 回归分析显示血浆 miRNA-21是 CAD 患者存在不稳定斑块的独立预测因子（P ＜0.05）。结论血浆miRNA-21水平升高预示 CAD 患者冠状动脉内斑块的不稳定状态,是预测 CAD 患者存在不稳定斑块的重要生物标志物之一。     

microRNAs 在肝病中的研究进展

microRNAs (miRNAs)是近年发现的一种以序列特异性方式转录后调控基因表达的非编码单链小分子RNA,长度为21～25个核苷酸。miRNAs可通过与靶基因mRNA的3’-非翻译区以完全互补或不完全互补的方式结合以调节靶基因的表达。miRNAs参与多种生物学调控过程,对疾病的诊断和治疗具有重要意义。本文就miRNAs的生物合成、作用机制及其在肝病中的研究进展作一综述。     

微小RNA在大鼠心脏逆重构中的变化

目的 构建大鼠心脏肥厚及移植模型来模拟临床心脏重构及逆重构过程,检测该过程中心脏胶原、转化生长因子-β(TGF-β)及微小RNA(miRNA)的改变,阐述TGF-β胶原轴在该过程中的变化并筛选部分可能参与该过程的miRNA.方法 实验Lewis大鼠分为4组,分别为假手术组、心脏肥厚组、肥厚移植组及单纯移植组.以动物超声心动图、免疫组织化学、心肌细胞横截面积检测、实时荧光定量逆转录聚合酶链反应(qRT-PCR)检测等方法对模型心肌细胞、心脏胶原和TGF-β的表达进行检测.miRNA芯片检测各组心脏组织miRNA的变化,对其中部分有意义的miRNA进行qRT-PCR验证,并通过miRNA靶点数据库分析其功能.结果 心脏肥厚组大鼠心脏重量、左心室重量、心室壁厚度和心肌横截面积均高于假手术组,而肥厚移植组均低于心脏肥厚组.单纯移植组心脏重量及心脏与整体重量比值均低于假手术组.心脏肥厚组胶原及TGF-β表达均高于假手术组,肥厚移植组中其表达高于心脏肥厚组.经基因芯片检测发现有82个miRNA在4个实验组中发生了2倍以上的变化,心脏肥厚组有1个miRNA高于假手术组,9个miRNA低于假手术组;肥厚移植组有26个miRNA高于心脏肥厚组,6个低于心脏肥厚组;单纯移植组有29个miRNA高于假手术组,11个低于假手术组.对其中6个miRNA进行验证,结果发现各组均发生了显著性变化,各组间△△CT差大于2倍,差异有统计学意义(P＜0.05).结论 大鼠心肌肥厚及卸负荷模型能较好的模拟心脏重构及逆重构过程.胶原和TGF-β在心脏肥厚模型中增加,且经卸负荷处理后增加更多.较多miRNA在肥厚过程中发生了改变,经对部分miRNA作用靶点的查找发现,miRNA可能通过不同的机制影响心脏重构及逆重构过程.

Abstract：

Objective To establish a reverse remodeling heart model in rats and observe collagen and TGF-β expression and relevant rmicroRNAs changes during reverse remodeling. Methods Lewis rats were divided into four groups including sham(NL, n = 10), abdominal aortic constriction(AAC, n = 10),heterotopic transplantation of abdominal aortic constriction(AAC-HT, n = 9)and heterotopic transplantation of normal heart(HT, n = 8). Left ventricular wall thickness and LV cavity were measured by echocardiography. The cardiomyocyte cross-sectional area(CSA)was determined on HE stained sections.Immunohistochemical and qRT-PCR were used to detect collagen and TGF-β expressions. miRNAs were detected by MicroRNA microarray. Results Heart weight, left ventricular wall thickness and CSA were significantly increased in AAC hearts compared to those in the NL and AAC-HT hearts. The collagen and TGF-β were increased in AAC hearts and further increased in AAC-HT hearts. miRNA microarray evidenced more than two folds changes on 82 miRNAs compared to NL(10 in AAC, 32 in AAC-HT and 40 in HT).Conclusion Rat abdominal aortic constriction and heterotopic transplantation could be used as a reverse remodeling heart model and significant collagen and TGF-β as well microRNA expression changes were evidenced in this model.     

MicroRNAs（miRNAs）——肿瘤形成过程中的重要参与者

MicroRNAs（miRNAs）是指一大类负调控基因表达的非编码蛋白质的小RNA。它们分布十分广泛,参与很多生物信号通路的调节,研究显示,一种miRNA所调节的靶基因就可达数百个。研究已证实,多种人类恶性肿瘤的发生、发展与miRNAs的异常表达有关,其作用相当于癌基因或抑癌基因。     

Infectious agents and lymphoma

In the past 25 years revelations on the genesis of human cancer have come at an increasing pace. Research on oncogenic infectious agents, especially viruses, has helped us to understand the process of malignant transformation of cells because the cellular events in viral-driven transformation mirror, often brilliantly, basic cellular processes that culminate in cancer, even those not associated with viruses. Infectious agents, especially viruses, account for several of the most common malignancies-up to 20% of all cancers. Some of these cancers are endemic, with a high incidence in certain geographic locations, but sporadic/lower incidence in other parts of the world. Lymphomas arise frequently in association with infectious agents such as Epstein-Barr virus, human immunodeficiency virus, human herpes virus 8, Helicobacter pylori, and hepatitis C virus. In this review, we will focus on the association between infectious agents and lymphomas, with a look at the molecular mechanisms they use to disturb cell regulation and eventually result in cancer.     

MicroRNAs：免疫系统的新型调节子

miRNAs是一类进化上保守的非编码小RNA,能在转录后水平对靶mRNAs进行降解或翻泽抑制,在多种牛物学过程中发挥重要调节作用.哺乳动物的免疫系统在抵抗感染、自身稳定和免疫监视方面发挥重要作用.为达到免疫应答和免疫耐受的恰当平衡,免疫反应的起始、终止和反应强度必须被严谨调节.相对于转录因子全开或全关的调节方式,miR-NAs更适合对免疫系统进行精细调节和定量调节.因为它们通过非常短的作用位点进行调节,在作用位点一个或少数几     

Dicer1 functions as a haploinsufficient tumor suppressor

While the global down-regulation of microRNAs (miRNAs) is a common feature of human tumors, its genetic basis is largely undefined. To explore this question, we analyzed the consequences of conditional Dicer1 mutation (Dicer1 “floxed” or Dicer1^fl) on several mouse models of cancer. Here we show Dicer1 functions as a haploinsufficient tumor suppressor gene. Deletion of a single copy of Dicer1 in tumors from Dicer1^fl/+ animals led to reduced survival compared with controls. These tumors exhibited impaired miRNA processing but failed to lose the wild-type Dicer1 allele. Moreover, tumors from Dicer1^fl/fl animals always maintained one functional Dicer1 allele. Consistent with selection against full loss of Dicer1 expression, enforced Dicer1 deletion caused inhibition of tumorigenesis. Analysis of human cancer genome copy number data reveals frequent deletion of DICER1. Importantly, however, the gene has not been reported to undergo homozygous deletion, suggesting that DICER1 is haploinsufficient in human cancer. These findings suggest Dicer1 may be an important haploinsufficient tumor suppressor gene and, furthermore, that other factors controlling miRNA biogenesis may also function in this manner.