lncRNA PCGEM1 strengthens anti-inflammatory and lung protective effects of montelukast sodium in children with cough-variant asthma

Abstract

Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-kB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-kB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.

Long Noncoding RNAs in the Regulation of Asthma: Current Research and Clinical Implications

“…Montelukast sodium is known as an effective drug to treat coughvariant asthma (CVA). Xu et al (2020) confirmed that this drug reduced inflammatory factor IL-4 and increased antiinflammatory factor IFN-g to enhance pulmonary function. With the further exploration in OVA-induced asthmatic murine, PCGEM1 was found to be downregulated and overexpressing PCGEM1 amplified the antiinflammatory effects of montelukast sodium, thus enhancing the lung function of the asthmatic murine.…”

The Role of Noncoding RNA in Airway Allergic Diseases through Regulation of T Cell Subsets

“…Feng et al [ 66 ] found that lncRNA-MEG3 was highly expressed in the serum of AS patients, and its elevated levels were correlated with the different inflammatory types and courses of AS. Xu et al [ 67 ] found that lncRNA PCGEM1 could enhance the anti-inflammatory and respiratory protective effects of montelukast sodium in children with cough variant AS by blocking the activation of the NF- κ B signaling pathway. In another study, significant variability in lncRNA expression profiles was found, and lncPVT1 was tested as a predictor of the occurrence of airway remodeling in AS patients by collecting smooth muscle cells of airway origin from AS patients and normal controls for transcriptome sequencing [ 68 ].…”

Long Noncoding RNA PCGEM1 Facilitates Tumor Growth and Metastasis of Osteosarcoma by Sponging miR‐433‐3p and Targeting OMA1

“…Through diverse functional mechanisms, PCGEM1 has a large effect on downstream genes and then regulates cancer cell proliferation, invasion and apoptosis 14,15 . PCGEM1 can influence other diseases, such as asthma and osteoarthritis 16,17 . More importantly, preclinical experiments and in vitro studies have shown the tremendous clinical potential of PCGEM1 18,19 .…”

“…14,15 PCGEM1 can influence other diseases, such as asthma and osteoarthritis. 16,17 More importantly, preclinical experiments and in vitro studies have shown the tremendous clinical potential of PCGEM1. 18,19 This literature demonstrates that PCGEM1 may be a potential target in cancer treatment, which inspired us to investigate the specific role and mechanism of PCGEM1 in OS.…”