Long noncoding RNAs at the crossroads of smoking, oxidative stress, inflammation, and lung disease.

Cigarette smoking is a well-recognized risk factor for chronic obstructive pulmonary disease (COPD) and lung cancer, but the underlying molecular mechanisms remain the subject of intense investigation. A large body of evidence has shown the role of long noncoding RNAs (lncRNAs) in the pathogenesis of smoke-related diseases. LncRNAs are > 200 nt-long functional transcripts with limited protein-coding potential, which are emerging as critical regulators of gene expression in a variety of biological processes. Exposure to cigarette smoke (CS) is known to cause widespread dysregulation of lncRNAs in lung tissues and immune cells, thus leading to disruption of cell homeostasis, and induction of oxidative stress and chronic inflammation. This review article discusses the interplay of lncRNAs, smoking, oxidative stress, immune response, and lung disease. First, we provide an overview of the functions and modes of action of lncRNAs in the regulation of gene expression at the epigenetic, transcriptional, and post-transcriptional levels. We then examine the different mechanisms by which tobacco-induced dysregulation of lncRNAs contributes to oxidative stress, chronic inflammation, and disease pathogenesis, while focusing on COPD and lung cancer. Finally, we highlight the importance of extending lncRNA research to new and emerging tobacco products and discuss the promises and pitfalls of lncRNAs as predictive biomarkers and prognostic targets. Understanding the intricate roles of lncRNAs in the pathogenesis of COPD and lung cancer can provide new avenues for advancing diagnostic tools and therapeutic strategies in the fight against these devastating smoke-associated diseases.