Russ Rebecca, Slack Frank J
Department of Molecular, Cellular and Developmental Biology, Yale University, P.O. Box 208103, New Haven, CT 06520, USA.
Pulm Med. 2012;2012:791234. doi: 10.1155/2012/791234. Epub 2011 Dec 1.
Dysregulation of microRNAs (miRNAs), particularly their downregulation, has been widely shown to be associated with the development of lung cancer. Downregulation of miRNAs leads to the overactivation of their oncogene targets, while upregulation of some miRNAs leads to inhibition of important tumor suppressors. Research has implicated cigarette smoke in miRNA dysregulation, leading to carcinogenesis. Cigarette smoke may lead to genetic or epigenetic damage to miRNAs, many of which map to fragile sites and some of which contain single nucleotide polymorphisms. Cigarette smoke may also cause dysregulation by affecting regulatory mechanisms controlling miRNA expression. Researchers have shown a correlation between smoke-exposure-induced dysregulation of miRNAs and age. Furthermore, dysregulation seems to be associated with intensity and duration of smoke exposure and duration of cessation. Longer exposure at a threshold level is needed for irreversibility of changes in expression. Better understanding of miRNA dysregulation may allow for improved biomonitoring and treatment regimens for lung cancer.
微小RNA（miRNA）失调，尤其是其下调，已被广泛证明与肺癌的发生发展相关。miRNA下调会导致其致癌基因靶点过度激活，而某些miRNA上调则会导致重要肿瘤抑制因子受到抑制。研究表明，香烟烟雾与miRNA失调有关，进而导致致癌作用。香烟烟雾可能会对miRNA造成基因或表观遗传损伤，其中许多定位到脆弱位点，有些还包含单核苷酸多态性。香烟烟雾还可能通过影响控制miRNA表达的调控机制导致失调。研究人员已表明，烟雾暴露引起的miRNA失调与年龄之间存在关联。此外，失调似乎与烟雾暴露的强度、持续时间以及戒烟时长有关。要使表达变化不可逆，需要在阈值水平上进行更长时间的暴露。对miRNA失调有更深入的了解可能有助于改善肺癌的生物监测和治疗方案。
