Gene Silencing Section, Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Toxicol Mech Methods. 2011 May;21(4):325-33. doi: 10.3109/15376516.2011.562759.
Tumor progression is the continual selection of variant subpopulations of malignant cells that have acquired increasing levels of genetic instability (Nowell Science 1976, 194, 23-28). This instability is manifested as chromosomal aneuploidy or translocations, viral integration or somatic mutations that typically affect the expression of a gene (oncogene) that is especially damaging to the proper function of a cell. With the recent discovery of non-coding RNAs such as microRNAs (miRNAs), the concept that a target of genetic instability must be a protein-encoding gene is no longer tenable. Over the years, we have conducted several studies comparing the location of miRNA genes to positions of genetic instability, principally retroviral integration sites and chromosomal translocations in the mouse as a means of identifying miRNAs of importance in carcinogenesis. In this current study, we have used the most recent annotation of the mouse miRome (miRBase, release 16.0), and several datasets reporting the sites of integration of different retroviral vectors in a variety of mouse strains and mouse models of cancer, including for the first time a model that shows a propensity to form solid tumors, as a means to further identify or define, candidate oncogenic miRNAs. Several miRNA genes and miRNA gene clusters stand out as interesting new candidate oncogenes due to their close proximity to common retroviral integration sites including miR-29a/b/c and miR106a~363. We also discussed some recently identified miRNAs including miR-1965, miR-1900, miR-1945, miR-1931, miR-1894, and miR-1936 that are close to common retroviral integration sites and are therefore likely to have some role in cell homeostasis.
肿瘤的进展是恶性细胞的亚群不断获得遗传不稳定性的选择（Nowell，Science，1976，194，23-28）。这种不稳定性表现为染色体非整倍体或易位、病毒整合或体细胞突变，这些通常会影响一个基因（癌基因）的表达，该基因对细胞的正常功能特别有害。随着非编码 RNA 如 microRNAs（miRNAs）的最近发现，遗传不稳定性的靶点必须是一个编码蛋白质的基因的概念不再可行。多年来，我们进行了几项研究，将 miRNA 基因的位置与遗传不稳定性的位置进行比较，主要是在小鼠中逆转录病毒整合位点和染色体易位，以确定在致癌作用中重要的 miRNAs。在本研究中，我们使用了小鼠 miRome（miRBase，版本 16.0）的最新注释，以及几个报告不同逆转录病毒载体在多种小鼠品系和小鼠癌症模型中整合位点的数据集，包括首次显示形成实体瘤倾向的模型，作为进一步鉴定或定义候选致癌 miRNA 的方法。由于其靠近常见逆转录病毒整合位点，几个 miRNA 基因和 miRNA 基因簇脱颖而出，成为有趣的新候选致癌基因，包括 miR-29a/b/c 和 miR106a~363。我们还讨论了一些最近发现的 miRNAs，包括 miR-1965、miR-1900、miR-1945、miR-1931、miR-1894 和 miR-1936，它们靠近常见逆转录病毒整合位点，因此可能在细胞内稳态中发挥作用。
