microRNA在大肠癌诊治中的研究进展

microRNA（微小RNA）是一类长度为17-25nt的单链非编码RNA,能够识别特定的目标mRNA,并在转录后水平对基因的表达起负调控作用。血液、粪便及大肠癌组织中的microRNA可以辅助诊断大肠癌和预测疾病复发。特异microRNA的过度表达或沉默与大肠癌的发生、发展有关。组织和血液中特异microRNA的表达不同,提示了其在大肠癌早期发现和筛检中的应用前景。众多研究提示,microRNA与大肠癌的化疗药物敏感性有关。此外,mi-croRNA在大肠癌发生、发展过程中的作用表明其可能是重要的基因治疗目标。     

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。     

微小核糖核酸在参与缺血/再灌注过程中的研究进展

微小核糖核酸(miRNA)是一种近年来发现的存在于真核生物中的非编码调控RNA,其作用机制主要是在转录后水平上调控基因的表达。不同miRNA在炎性反应以及组织缺血/再灌注(I/R)过程中的表达水平有不同程度的变化,炎性反应是介导I/R损伤的重要因素之一,这一现象初步揭示了miRNA在I/R过程中扮演着重要的角色。深入研究将miRNA早期诊断和治疗I/R损伤有重要的临床意义。