Long Noncoding Transcriptome in Chronic Obstructive Pulmonary Disease

Abstract

Chronic airway inflammation from recurring exposures to noxious environmental stimuli results in a progressive and irreversible airflow limitation and the lung parenchymal damage that characterizes chronic obstructive pulmonary disease (COPD). The large variability observed in the onset and progression of COPD is primarily driven by complex gene-environment interactions. The transcriptomic and epigenetic memory potential of lung epithelial and innate immune cells drive responses, such as mucus hyperreactivity and airway remodeling, that are tightly regulated by various molecular mechanisms, for which several candidate susceptibility genes have been described. However, the recently described noncoding RNA species, in particular the long noncoding RNAs, may also have an important role in modulating pulmonary responses to chronic inhalation of toxic substances and the development of COPD. This review outlines the features of long noncoding RNAs that have been implicated in regulating the airway inflammatory responses to cigarette smoke exposure and their possible association with COPD pathogenesis. As COPD continues to debilitate the increasingly aging population and contribute to higher morbidity and mortality rates worldwide, the search for better biomarkers and alternative therapeutic options is pivotal.

Keywords: cigarette smoke; inflammation; lncRNAs; mitochondria; senescence.

Figure 1.

Tobacco smoke exposure alters the expression and functions of long noncoding RNAs, which could lead to augmented chronic obstructive pulmonary disease pathologies, including those associated with mitochondrial dysfunction, chronic inflammation, mucus dysregulation, epigenetic alterations, and cellular senescence. ANRIL = antisense noncoding RNA in the INK 4 locus; COPD = chronic obstructive pulmonary disease; HOTAIR = HOX (Homeobox gene) transcript antisense RNA; LIPCAR = long intergenic noncoding RNA predicting cardiac remodeling; lncRNAs = long noncoding RNAs; M-AS1 = Alpha-2-macroglobulin protein antisense RNA 1 (A2M-AS1); MALAT1 = metastasis-associated lung adenocarcinoma transcript 1; MANTIS = a nuclear lncRNA n342419 that facilitates endothelial angiogenesis; MEG3 = maternally expressed gene 3; MUC5B-AS1 = mucin-5 subtype B antisense RNA 1; PINT = P53 induced Transcript lincRNA; SAL-RNA = senescence-associated long noncoding RNA; SNHG-16 = a small nucleolar RNA host gene 16; Sox2ot = SRY (sex determining region Y)-box-2 overlapping transcript; Xist = X-inactive specific transcript.