微小RNA与肿瘤耐药

 【摘要】　微小RNA （miRNA）是近年来在真核生物中发现的、在转录后水平负调控基因表达的一类长约22个核苷酸的非编码小分子RNA。miRNA生物学效应广泛,与细胞生长、凋亡、新陈代谢和信号转导等密切相关。已报道miRNA在各种肿瘤中表达失常,可能发挥着癌基因和抑癌基因的双重作用,同时越来越多的研究表明miRNA在调节肿瘤细胞对抗肿瘤药物耐药方面发挥着重要作用。系统深入地研究miRNA在肿瘤耐药中的机制,将为发展基于miRNA逆转肿瘤耐药的治疗策略提供重要的依据。     

实时荧光定量PCR方法检测石蜡包埋组织microRNA表达的方法探讨

目的:探讨从石蜡包埋组织中运用实时荧光定量PCR(RQ-PCR)方法检测microRNA表达的可靠性和敏感性。方法:选取2005年至2010年从石河子大学医学院第一附属医院、新疆伊犁哈萨克族自治州友谊医院收集的97例福尔马林固定、石蜡包埋食管癌组织样本,提取组织总RNA,RT-PCR逆转录为cDNA,实时荧光定量PCR法检测microRNA表达。结果:97例食管癌组织样本中,RNA提取成功90例,7例失败,运用实时荧光定量PCR成功检测了83例microRNA表达,7例检测不准确。RNA提取成功率明显高于失败率,实时荧光定量PCR检出的定量准确例数高于定量不准确例数,P<0.05,差异具有统计学意义。结论:实时荧光定量PCR(RQ-PCR)方法是检测石蜡包埋组织中microRNA表达的一种有效方法。     

Tolerance versus immune response — MicroRNAs as important elements in the regulation of the HLA-G gene expression

HLA-G is a class Ib HLA which has gained much attention due to its multiple functions on the immune system. HLA-G exerts several immunomodulatory effects, being beneficially implicated in embryo implantation and fetal survival but, conversely, being potentially detrimental in tumors and viral infections. Such a two-edged sword behavior suggest that HLA-G expression is under tight regulation. However, to date, little is known about the regulation of this gene and previous works have been unable to well correlate HLA-G regulation at the mRNA level with the polymorphic variants at the genomic level. Here we present the hypothesis that an element, which was until now neglected, might play a role in HLA-G expression regulation: MicroRNAs might participate in the regulation of the HLA-G gene expression through a putative microRNA binding site at its 3′ UTR region. Inside the 20 nt region of this microRNA binding site lies a C/G polymorphism, which was shown to be responsible for differential microRNA binding affinity and translation suppression. The role of microRNA binding on the regulation of HLA-G gene expression (and therefore on tolerance versus immune response) can be easily tested through relatively simple steps: Confirming the expression of those three complementary microRNAs in human cells which express HLA-G, followed by examination of the correlation between HLA-G mRNA and protein production controlling for HLA-G genotypes and microRNA levels; finally, selective inhibition of microRNA activity with anti-sense oligos restoring HLA-G production would access microRNA influence on HLA-G expression which, if confirmed, might help in the development of strategies to the management of several conditions in which HLA-G is involved, including pregnancy complications, transplantation, and cancer.     

The tumor-promoting activity of 2-acetylaminofluorene is associated with disruption of the p53 signaling pathway and the balance between apoptosis and cell proliferation

The aromatic amine 2-acetylaminofluore (2-AAF) is a powerful complete genotoxic rat liver carcinogen that induces tumors without any additional interventions. While the tumor-initiating genotoxic activity of 2-AAF is well established, its tumor-promotion activity is far less understood. It is believed that the tumor-promoting property of 2-AAF is associated with selective enhancement of cell replication and sustained suppression of apoptosis in initiated cells. In the present study, we investigated the underlying mechanisms of tumor-promoting events induced by 2-AAF-exposure. Male Sprague-Dawley rats were fed NIH-31 diet containing 0.02% of 2-AAF for 12 and 24 weeks, and the expression pattern of genes associated with the p53-signaling pathway and microRNA genes was determined in the livers of control and 2-AAF-fed rats. The results indicate that the tumor-promoting property of 2-AAF during hepatocarcinogenesis is associated predominantly with the up-regulation of anti-apoptotic growth-related genes and down-regulation of expression of pro-apoptotic genes. This disrupts the balance between cell proliferation and apoptosis, which leads to consequential unrestricted cell proliferation, especially of initiated cells. Also, the long-term-administration of 2-AAF resulted in disruption of regulatory miR-34a-p53 feed-back loop that mediates apoptosis. This was evidenced by an increased expression of miR-34a in response to genotoxic effects of 2-AAF in the absence of p53 up-regulation, and loss of regulatory control of mir-34a on SIRT1 function. Additionally, the livers of 2-AAF-exposed rats were characterized by the substantial deregulation of expression of miR-18, miR-21, miR-182, and miR-200 family, microRNAs involved in control of apoptosis/cell proliferation and cell-cell contact pathways, two major pathways disrupted during the promotion stage of hepatocarcinogenesis.     

髓母细胞瘤相关miRNA的研究进展

髓母细胞瘤（medulloblastoma）是儿童颅内恶性程度极高的常见肿瘤之一,具体病因不明,预后极差。现阶段随着髓母细胞瘤分子遗传学研究的逐步深入．microRNAfmiRNA）更成为研究的热点。本文将就miRNA与髓母细胞瘤的关系作一综述。     

MicroRNA及其与妇科肿瘤相关性研究进展

近些年来,一类新的非蛋白质编码MicroRNA(miRNA)的出现,为肿瘤研究提供了新的思路。研究发现,肿瘤细胞与正常组织来源细胞间miRNA表达谱具有明显差异,且多数miRNA基因位于与肿瘤形成的相关性脆弱基因位点,从而推测miRNA在肿瘤形成过程中可能扮演着重要的角色。而且,miRNA的异常表达与多种癌症的发生密切相     

MicroRNA与肝癌的相关研究

肝癌是消化系统的常见恶性肿瘤,早期诊断困难,治疗手段有限,总体预后较差。近年来随着对MicroRNA深入研究,人们逐渐意识到MicroRNA与肝癌的发生、发展、转移等密切相关,并且在肝癌的早期诊断、治疗及预后评估中有着广阔的前景。本文就近年来关于MicroRNA与肝癌的相关研究作一概述。