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微小RNA与癌症的特征

MicroRNAs and the hallmarks of cancer.

作者信息

Dalmay T, Edwards D R

机构信息

School of Biological Sciences, University of East Anglia, Norwich, UK.

出版信息

Oncogene. 2006 Oct 9;25(46):6170-5. doi: 10.1038/sj.onc.1209911.

Abstract

It has become clear that particular microRNAs (miRNAs) function either as tumour suppressors or oncogenes, whose loss or overexpression, respectively, has diagnostic and prognostic significance. In several cases, miRNAs have been shown to affect target genes that are involved in the control of cell proliferation and apoptosis. However, malignant tumours display additional traits beyond the acquisition of enhanced growth potential and decreased cell death. Malignant disease is associated with altered tumour-host interactions leading to sustained angiogenesis and the ability to invade and metastasize. It is possible that miRNAs may act as master regulators of these aspects of tumour biology. Bioinformatic analysis of putative miRNA binding sites has indicated several novel potential gene targets of cancer-associated miRNAs that function in aspects of cell adhesion, neovascularization and tissue invasion. Among others, we speculate that miRNAs may find new roles in the regulation of E-cadherin, integrin alphavbeta3, hypoxia-inducible factor-1alpha, syndecan-1, lysyl oxidase, adamalysin metalloproteinase-17, tissue inhibitors of metalloproteinase-3, c-Met and CXCR-4 that underpin the tissue architectural changes associated with malignancy.

摘要

现已明确,特定的微小RNA(miRNA)发挥着肿瘤抑制因子或癌基因的作用,其缺失或过表达分别具有诊断和预后意义。在一些情况下,miRNA已被证明会影响参与细胞增殖和凋亡调控的靶基因。然而,恶性肿瘤除了具有增强的生长潜能和降低的细胞死亡能力外,还表现出其他特征。恶性疾病与肿瘤-宿主相互作用的改变有关,导致持续的血管生成以及侵袭和转移能力。miRNA有可能作为肿瘤生物学这些方面的主要调节因子。对假定的miRNA结合位点进行生物信息学分析,已表明癌症相关miRNA的几个新的潜在基因靶点在细胞黏附、新血管形成和组织侵袭方面发挥作用。其中,我们推测miRNA可能在E-钙黏蛋白、整合素αvβ3、缺氧诱导因子-1α、多配体蛋白聚糖-1、赖氨酰氧化酶、解整合素金属蛋白酶-17、金属蛋白酶组织抑制剂-3、c-Met和CXCR-4的调控中发挥新作用,这些因子是与恶性肿瘤相关的组织结构变化的基础。

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