NcRNAs as therapeutic target for diabetes and its complications
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Alireza Nasr Esfahani,1,* Setare Samizade,2 Nooshin Naghsh,3
1. Department of Molecular & Cell Biochemistry, Falavarjan Branch, Islamic Azad University
2. Department of Molecular & Cell Biochemistry, Falavarjan Branch, Islamic Azad University
3. Department of Biologoy, Falavarjan Branch, Islamic Azad University, Isfahan, Iran
- Introduction: Diabetes is one of the most common metabolic diseases
that leads to the induction of many health complications. In developed countries, it is the main cause of blindness, end-stage renal failure and non-traumatic amputation of the lower limbs. Diagnosis and treatment progression have key role in exploration of biomarkers for diabetes. A novel group of gene expression regulators is a class of small non-coding RNAs of 18-24 oligonucleotides in length, function to post transcriptionally regulate protein expression termed ncrRNAs which can cause gene silencing through degradation of target mRNAs or blocking of translation. Dysregulated expression of ncRNAs include microRNAs (miRNAs) and Long non coding RNAs (lncRNA) has been shown in various human diseases, such as diabetes.so this study aims to investigate the relationship between diabetes and ncRNAs in associated pathways.
- Methods: By using mirbase, HMDD and miRdSNP, miRNA properties were obtained. The miRTarBase, MIRWALK2.0 and TargetScan, 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 diabetes were interpreted. The gene network was obtained through GENE MANIA.
- Results: We identified hsa-miR-23a-5p as the best miRNA, its target genome and associated cell signaling pathways. Then, the findings presented that this miRNA had a key role in polyol pathway, hexosamine pathway, PKCs signaling, oxidative stress, AGEs pathway, PARP pathway, MAPK pathway, NF-κB signaling, hedgehog pathways, TNF-α signaling, cyclooxygenase pathway, interleukins, lipoxygenase pathway, nerve growth factor, Wnt pathway, autophagy, and GSK3 signaling that may be accounted for the pathogenesis and progression of diabetic. Next, we used series of bioinformatics software to obtain the lncRNAs and their relationship with over expression gene and diabetes.
- Conclusion: : Diabetes is a complicated and life-threatening disease, which affects ∼30-90% of diabetic patients across the world. Multiple signaling pathways are integrally accountable for the development and pathogenesis of diabetes. The result demonstrated that has-mir23a-5p inhibits 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. The long non-coding RNA metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is highly phylogenetic and conserved in mammals. MALAT1 knockout decreased the expression levels of total and phosphorylated p38 and reduced the apoptosis of rat CEP cells. The results obtained in the present study indicated that MALAT1 may serve as an important therapeutic target for diabetic patients. This new molecular methods for the accurate treatment of diabetes is suggested.
- Keywords: Diabetes, MAPK pathway, MicroRNA, TNF pathway, LncRNA
