Noncoding RNAs in Tumor Angiogenesis
Noncoding RNAs in Tumor Angiogenesis
复制标题
DOI：
10.1007/978-981-10-1498-7_8
复制
发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Yang, Burton B.
中科院分区：
文献类型：
--
作者：
Khorshidi, Azam;Dhaliwal, Preet;Yang, Burton B.
实体瘤需要血管生成生长超过2mm的大小。在大多数情况下，肿瘤细胞会经历血管生成转换，并分泌从现有血管中生成新毛细血管所需的物质。肿瘤血管生成是由促血管生成因子（VEGF/VEGFR, PDGF/PDGFR）和抗血管生成因子（TSP-1/TSP-2）在肿瘤微环境中复杂的相互作用驱动的。此外，基质金属蛋白酶（MMPs）和组织金属蛋白酶抑制剂（TIMPs）对组织重塑和降解的控制有助于肿瘤血管生成。此外，控制细胞运动和维持或促进缺氧的肿瘤抑制因子或癌基因（hif和MYC）也在肿瘤血管生成中积极发挥作用。非编码rna (ncRNAs)，包括microRNAs，是一类以转录后方式控制基因表达的新型调控分子。MicroRNAs调节重要的生理过程，如增殖、凋亡和分化，以及包括肿瘤发生在内的病理条件。越来越多的证据表明，microrna通过靶向重要的血管生成因子和信号分子直接调节血管生成过程。了解microrna调控血管生成的分子机制非常重要，因为它们具有潜在的治疗潜力，可能会改善癌症患者的预后。此外，基因组中还发现了长链非编码rna （long noncoding RNAs, lncRNAs）等在血管生成中具有调控作用的ncRNAs。然而，绝大多数lncrna的作用机制目前尚不清楚。对于少数功能水平的lncrna，越来越多的证据表明它们在恶性疾病中发挥重要作用。本章将介绍血管生成的功能和机制。
Solid tumors require angiogenesis to grow beyond 2 mm in size. In most cases, tumor cells undergo angiogenic switch and secrete substances that are required for generation of new capillary sprouting from existing blood vessels. Tumor angiogenesis is driven by a complex interplay between pro-angiogenic (VEGF/VEGFR, PDGF/PDGFR) and anti-angiogenic factors (TSP-1/TSP-2) within the tumor microenvironment. In addition, control of tissue remodeling and degradation by matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) contribute to tumor angiogenesis. Furthermore, tumor suppressors or oncogenes that control cellular motility and maintain or promote hypoxia (HIFs and MYC) are also actively playing roles in tumor angiogenesis. Noncoding RNAs (ncRNAs), including microRNAs, are a novel class of regulatory molecules that control the gene expression in a posttranscriptional manner. MicroRNAs regulate important physiological processes, such as proliferation, apoptosis, and differentiation, as well as pathological conditions including oncogenesis. Accumulating evidence suggests that microRNAs directly modulate the process of angiogenesis by targeting important angiogenic factors and signaling molecules. Understanding the molecular mechanism behind the regulation of angiogenesis by microRNAs is important due to their therapeutic potential which may lead to improving outcome for cancer patients. Besides, ncRNAs with a regulatory role in angiogenesis, such as long noncoding RNAs (lncRNAs), have been identified in the genome. However, the mechanisms of the vast majority of lncRNAs are currently unknown. For the few lncRNAs characterized at the functional level, accumulating evidence shows that they play important roles in malignant diseases. The function and mechanism in angiogenesis will be described in this chapter.