Cancer Epigenomics and Lung Diseases Laboratory-12 (UNAM-INER), Biomedicine Research Unit (UBIMED), Facultad de Estudios Superiores (FES)-Iztacala, Universidad Nacional Autónoma de México (UNAM), Mexico State, Mexico.
Thoracic Oncology Unit and Laboratory of Personalized Medicine, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico.
Clin Epigenetics. 2017 Sep 8;9:98. doi: 10.1186/s13148-017-0398-3. eCollection 2017.
Respiratory diseases hold several genome, epigenome, and transcriptional aberrations as a cause of the accumulated damage promoted by, among others, environmental risk factors. Such aberrations can also come about as an adaptive response when faced with therapeutic oncological drugs. In epigenetic terms, aberrations in DNA methylation patterns, histone code marks balance, and/or chromatin-remodeling complexes recruitment, among Polycomb Repressive Complex-2 (PRC2) versus Trithorax (TRX) Activator Complex, have been proposed to be affected by several previously characterized functional long non-coding RNAs (lncRNAs). Such molecules are involved in modulating and/or controlling lung cancer epigenome and genome expression, as well as in malignancy and clinical progression in lung cancer. Several recent reports have described diverse epigenetic modifications in lung cancer cells and solid tumors, among others genomic DNA methylation and post-translational modifications (PTMs) on histone tails, as well as lncRNAs patterns and levels of expression. However, few systematic approaches have attempted to demonstrate a biological function and clinical association, aiming to improve therapeutic decisions in basic research and lung clinical oncology. A widely used example is the lncRNA HOTAIR and its functional histone mark H3K27me3, which is directly associated to the PRC2; however, few systematic pieces of solid evidence have been experimentally performed, conducted and/or validated to predict lung oncological therapeutic efficacy. Recent evidence suggests that chromatin-remodeling complexes accompanied by lncRNAs profiles are involved in several comprehensive lung carcinoma clinical parameters, including histopathology progression, prognosis, and/or responsiveness to unique or combined oncological therapies. The present manuscript offers a systematic revision of the current knowledge about the major epigenetic aberrations represented by changes in histone PTMs and lncRNAs expression levels and patterns in human lung carcinomas in cancer drug-based treatments, as an important comprehensive knowledge focusing on better oncological therapies. In addition, a new future direction must be refocusing on several gene target therapies, mainly on pharmaceutical EGFR-TKIs compounds, widely applied in lung cancer, currently the leading cause of death by malignant diseases.
呼吸系统疾病存在多种基因组、表观基因组和转录异常，这些异常是由环境危险因素等因素导致的累积损伤的原因之一。这些异常也可能是治疗性肿瘤药物作用下的适应性反应。在表观遗传学方面，DNA 甲基化模式、组蛋白密码标记平衡和/或染色质重塑复合物募集的异常，在多梳抑制复合物 2 (PRC2)与三翼旋转酶 (TRX)激活复合物之间，已经被提出受到几个先前表征的功能性长非编码 RNA (lncRNA) 的影响。这些分子参与调节和/或控制肺癌的表观基因组和基因组表达，以及肺癌的恶性肿瘤和临床进展。最近的几份报告描述了肺癌细胞和实体肿瘤中的多种表观遗传修饰，包括基因组 DNA 甲基化和组蛋白尾部的翻译后修饰 (PTMs)，以及 lncRNA 模式和表达水平。然而，很少有系统的方法试图证明生物学功能和临床相关性，旨在改善基础研究和肺癌临床肿瘤学中的治疗决策。一个广泛使用的例子是 lncRNA HOTAIR 及其功能性组蛋白标记 H3K27me3，它直接与 PRC2 相关；然而，很少有系统的证据被实验性地进行、进行和/或验证，以预测肺癌肿瘤治疗的疗效。最近的证据表明，伴随 lncRNA 谱的染色质重塑复合物参与了几个全面的肺癌临床参数，包括组织病理学进展、预后和/或对独特或联合肿瘤治疗的反应性。本文系统地回顾了人类肺癌在癌症药物治疗中代表组蛋白 PTM 和 lncRNA 表达水平和模式变化的主要表观遗传异常的最新知识，作为一个重要的综合知识，重点是更好的肿瘤治疗。此外，必须重新关注几种基因靶向治疗，主要是针对广泛应用于肺癌的制药 EGFR-TKIs 化合物，目前肺癌是恶性疾病死亡的主要原因。
