MicroRNA regulation of allergic inflammation and asthma in TNF pathway

MicroRNA regulation of allergic inflammation and asthma in TNF pathway
Alireza Nasr Isfahani,^1,* Setare Samizadeh,² Fatemeh Abedi dorcheh,³ Anasik Karbedian hajiabadi ,⁴
1. Department of Biochemistry, Islamic Azad University, Najafabad Branch, Iran
2. Department of Biochemistry, Islamic Azad University, Najafabad Branch, Iran
3. Departman of Biotechnology,School of Bioscience and biotechnology,Shahid Ashrafi University Of Isfahan,Sepahan shahr,Iran
4. Department of Microbiology, School of Biological Sciences, Islamic Azad University of Falavarjan,Iran
Introduction: Allergic asthma is an inflammatory disease of the airways characterized by recurrent episodes of wheezing and bronchoconstriction which frequently occur together. Chronic inflammation may finally lead to structural damage followed by airway remodeling. Diagnosis and treatment progression have key role in exploration of biomarkers for allergic rhinitis and allergic asthma. A novel group of gene expression regulators is a class of small non-coding RNAs of 18-24 nucleotides in length, function to post transcriptionally regulate protein expression termed microRNAs (miRNAs). miRNAs can cause gene silencing through degradation of target mRNAs or blocking of translation. Dysregulated expression of miRNAs has been shown in various human diseases, such allergic asthma. Although studies of miRNAs in inflammatory upper airway diseases are relatively new and few, emerging evidence implicates an involvement of miRNAs in shaping the inflammation pattern in upper airways.so this study aims to investigate the relationship between allergic asthma and miRNAs in associated pathways.
Methods: By using mirbase, HMDD and miRdSNP, miRNA properties were obtained. The miRTarBase, MIRWALK2.0, TargetScan, DIANA Tools target genes were identified. Venn diagram used to identify common target genes between MiRNAs. Using DAVID and KEGG, signal paths were obtained and the pathways associated with allergic asthmacer were interpreted. The gene network was obtained through GENE MANIA.
Results: The result demonstrated that mir199a, mir-27a, mir-374b and mir-374a inhibit Ras by blocking Raf-1,MEK1/2 which active ERK,SRF and c-fos through phosphorylation in MAPK and Gap junction pathways. Mentioned microRNAs prevent allergic asthma by inhibiting (IL1b-IL6-IL15-lif-tnf) by blocking MKK4/7, JUNK1/2 in TNF pathway .
Conclusion: TNF pathway has been implicated in many aspect of the airway pathology allergic asthma in which mir199a, mir-27a,mir-374b and mir-374a prevent inflammation and allergic reaction by inhibiting leukocyte activation and inflammatory cytokines.so miRNAs can be act as potential biomarkers in TNF pathway by inhibiting allergic asthma progression.
Keywords: Allergic asthma, MAPK pathway , MicroRNA, TNF pathway