Abstract
Evidence of the involvement of long noncoding RNAs (lncRNAs) in the pathogenesis of chronic obstructive pulmonary disease (COPD) is growing but still largely unknown. This study aims to explore the expression, functions and molecular mechanisms of Fantom3_F830212L20, a lncRNA that transcribes in an antisense orientation to Nqo1.We name this lncRNA as Nqo1 antisense transcript 1 (Nqo1-AS1). The distribution, expression level and protein coding potential of Nqo1-AS1 were determined. The effects of Nqo1-AS1 on cigarette smoke (CS)-induced oxidative stress were also evaluated. The results showed that Nqo1-AS1 were mainly located in the cytoplasm of mouse alveolar epithelium and had a very low protein coding potential. Nqo1-AS1 (or its human homologue) was increased with the increase of CS exposure. Nqo1-AS1 overexpression enhanced the mRNA and protein levels of Nqo1 and Serpina1 mRNA expression, and attenuated CS-induced oxidative stress, whereas knockdown of Nqo1-AS1 significantly decreased Nqo1 and Serpina1 mRNA expressions, and aggravated CS-induced oxidative stress. Nqo1-AS1 increased Nqo1 mRNA stability and upregulated Nqo1 expression through antisense pairing with Nqo1 3′UTR. In conclusion, these results suggest that Nqo1-AS1 attenuates CS-induced oxidative stress by increasing Nqo1 mRNA stability and upregulating Nqo1 expression, which might serve as a novel approach for the treatment of COPD.
Highlights
Chronic obstructive pulmonary disease (COPD) is a lung disease that is usually progressive degenerative and characterized by persistent respiratory symptoms and incompletely reversible expiratory airflow limitation (Duffy and Criner, 2019; Gu et al, 2021), which is a leading cause of death and disability worldwide (Wang et al, 2018; Riley and Sciurba, 2019)
We further proved that NAD(P)H quinone oxidoreductase 1 (Nqo1)-AS1 was upregulated in lung tissues of mice exposed to cigarette smoke (CS) and the mle-12 cells treated with CSE, and its human homologue expression was upregulated in peripheral blood mononuclear cells (PBMCs) of patients with chronic obstructive pulmonary disease (COPD) when compared to those of the control group
We named this long noncoding RNAs (lncRNAs) as Nqo1 antisense transcript 1 (Nqo1-AS1) (Figure 1A).RNA ISH revealed that the majority of Nqo1-AS1 expression existed in alveolar epithelial cells of mouse with chronic CS exposure, whereas the positive staining was occasionally observed in mouse without CS exposure (Figure 1B)
Summary
Chronic obstructive pulmonary disease (COPD) is a lung disease that is usually progressive degenerative and characterized by persistent respiratory symptoms and incompletely reversible expiratory airflow limitation (Duffy and Criner, 2019; Gu et al, 2021), which is a leading cause of death and disability worldwide (Wang et al, 2018; Riley and Sciurba, 2019). It is demonstrated that NQO1 expression is the activation of aryl hydrocarbon receptor (AhR) pathway by propolis, which promotes lung repair in a mouse emphysema model caused by CS exposure (Barroso et al, 2017).studies have proved that NQO1 P187S polymorphisms is determined as risk genotype in children with obstructive bronchitis, whose mother smoke actively during their pregnancies. Previous studies have reported that Nqo expression in lung tissue was upregulated by CS exposure (Adair-Kirk et al, 2008; Shahdoust et al, 2013).Recently, a study showed that overexpression of Nqo was able to increase scavenging of superoxide in Chinese hamster ovary cells, suggesting that Nqo plays a critical role in antioxidant protection (Ross and Siegel, 2017). The role of Nqo in COPD is still unknown
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