LncRNA Nqo1-AS1 Attenuates Cigarette Smoke-Induced Oxidative Stress by Upregulating its Natural Antisense Transcript Nqo1

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.

[1]  X. Su,et al.  Clinical features and prognostic analysis of patients with Aspergillus isolation during acute exacerbation of chronic obstructive pulmonary disease , 2021, BMC Pulmonary Medicine.

[2]  Nianzhi Zhang,et al.  LINC00987 Ameliorates COPD by Regulating LPS-Induced Cell Apoptosis, Oxidative Stress, Inflammation and Autophagy Through Let-7b-5p/SIRT1 Axis , 2020, International journal of chronic obstructive pulmonary disease.

[3]  Wei Wei,et al.  Mechanisms by Which the MBD2/miR-301a-5p/CXCL12/CXCR4 Pathway Regulates Acute Exacerbations of Chronic Obstructive Pulmonary Disease , 2020, International journal of chronic obstructive pulmonary disease.

[4]  K. Zhu,et al.  Significant association of PKM2 and NQO1 proteins with poor prognosis in breast cancer. , 2020, Pathology, research and practice.

[5]  Yajing Gao,et al.  Lnc-BAZ2B promotes M2 macrophage activation and inflammation in asthmatic children through stabilizing BAZ2B pre-mRNA. , 2020, The Journal of allergy and clinical immunology.

[6]  Lixia Dong,et al.  The clinical value of lncRNA MALAT1 and its targets miR‐125b, miR‐133, miR‐146a, and miR‐203 for predicting disease progression in chronic obstructive pulmonary disease patients , 2020, Journal of clinical laboratory analysis.

[7]  M. Malaise,et al.  Exosomal Long Non-Coding RNAs in Lung Diseases , 2020, International journal of molecular sciences.

[8]  P. Barnes.  Oxidative stress-based therapeutics in COPD , 2020, Redox biology.

[9]  M. Blanchette,et al.  Inter-dependent Centrosomal Co-localization of the cen and ik2 cis-Natural Antisense mRNAs in Drosophila. , 2020, Cell reports.

[10]  M. Guo,et al.  Long Noncoding RNA AFAP1-AS1 Promotes Cell Proliferation and Metastasis via the miR-155-5p/FGF7 Axis and Predicts Poor Prognosis in Gastric Cancer , 2020, Disease markers.

[11]  Yi Wang,et al.  SPAG5‐AS1 inhibited autophagy and aggravated apoptosis of podocytes via SPAG5/AKT/mTOR pathway , 2020, Cell proliferation.

[12]  Liyun Ye,et al.  Long non-coding RNA MEG3 regulates CSE-induced apoptosis and inflammation via regulating miR-218 in 16HBE cells. , 2020, Biochemical and biophysical research communications.

[13]  F. Dasí,et al.  Oxidative Stress in COPD , 2019, Journal of clinical medicine.

[14]  P. Ran,et al.  lncRNA COPDA1 Promotes Airway Smooth Muscle Cell Proliferation in Chronic Obstructive Pulmonary Disease. , 2019, American journal of respiratory cell and molecular biology.

[15]  J. Xu,et al.  Hydrogen sulfide attenuates cigarette smoke-induced airway remodeling by upregulating SIRT1 signaling pathway , 2019, Redox biology.

[16]  Zhangli Hu,et al.  Overexpression Of hsa-miR-664a-3p Is Associated With Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease Via Targeting FHL1 , 2019, International journal of chronic obstructive pulmonary disease.

[17]  Tania L. Slatter,et al.  Long Non-coding RNA ANRIL in the Nucleus Associates With Periostin Expression in Breast Cancer , 2019, Front. Oncol..

[18]  Young‐Hee Kang,et al.  Dried Yeast Extracts Curtails Pulmonary Oxidative Stress, Inflammation and Tissue Destruction in a Model of Experimental Emphysema , 2019, Antioxidants.

[19]  D. Boothman,et al.  NQO1 targeting prodrug triggers innate sensing to overcome checkpoint blockade resistance , 2019, Nature Communications.

[20]  Hao Wu,et al.  Ai-lncRNA EGOT enhancing autophagy sensitizes paclitaxel cytotoxicity via upregulation of ITPR1 expression by RNA-RNA and RNA-protein interactions in human cancer , 2019, Molecular Cancer.

[21]  G. Criner,et al.  Chronic Obstructive Pulmonary Disease: Evaluation and Management. , 2019, The Medical clinics of North America.

[22]  F. Sciurba,et al.  Diagnosis and Outpatient Management of Chronic Obstructive Pulmonary Disease: A Review , 2019, JAMA.

[23]  Thanyaluck Sriboonreung,et al.  Preliminary study: comparative effects of lung volume therapy between slow and fast deep-breathing techniques on pulmonary function, respiratory muscle strength, oxidative stress, cytokines, 6-minute walking distance, and quality of life in persons with COPD , 2018, International journal of chronic obstructive pulmonary disease.

[24]  Sarah E. Holton,et al.  A natural antisense lncRNA controls breast cancer progression by promoting tumor suppressor gene mRNA stability , 2018, PLoS genetics.

[25]  Jiasheng Xu,et al.  The research progress of LncRNA involved in the regulation of inflammatory diseases , 2018, Molecular immunology.

[26]  N. Zhong,et al.  Hydrogen gas inhalation protects against cigarette smoke-induced COPD development in mice. , 2018, Journal of thoracic disease.

[27]  Chenting Zhang,et al.  Long non-coding RNA expression patterns in lung tissues of chronic cigarette smoke induced COPD mouse model , 2018, Scientific Reports.

[28]  Yongjian Xu,et al.  Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study , 2018, The Lancet.

[29]  V. Bours,et al.  Natural Antisense Transcripts: Molecular Mechanisms and Implications in Breast Cancers , 2018, International journal of molecular sciences.

[30]  Jian Gao,et al.  Nrf2 antioxidant pathway suppresses Numb-mediated epithelial–mesenchymal transition during pulmonary fibrosis , 2018, Cell Death & Disease.

[31]  V. Lagente,et al.  Propolis reversed cigarette smoke-induced emphysema through macrophage alternative activation independent of Nrf2. , 2017, Bioorganic & medicinal chemistry.

[32]  D. Ross,et al.  Functions of NQO1 in Cellular Protection and CoQ10 Metabolism and its Potential Role as a Redox Sensitive Molecular Switch , 2017, Front. Physiol..

[33]  Z. Yao,et al.  The liver-enriched lnc-LFAR1 promotes liver fibrosis by activating TGFβ and Notch pathways , 2017, Nature Communications.

[34]  Feifei Qiu,et al.  Impacts of cigarette smoking on immune responsiveness: Up and down or upside down? , 2016, Oncotarget.

[35]  R. de Cabo,et al.  Novel RNA-binding activity of NQO1 promotes SERPINA1 mRNA translation. , 2016, Free radical biology & medicine.

[36]  Ebrahim Hajizadeh,et al.  Finding genes discriminating smokers from non-smokers by applying a growing self-organizing clustering method to large airway epithelium cell microarray data. , 2013, Asian Pacific journal of cancer prevention : APJCP.

[37]  A. El-Kadi,et al.  Effect of mercury on aryl hydrocarbon receptor-regulated genes in the extrahepatic tissues of C57BL/6 mice. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[38]  T. Betsuyaku,et al.  Distal airways in mice exposed to cigarette smoke: Nrf2-regulated genes are increased in Clara cells. , 2008, American journal of respiratory cell and molecular biology.