Cross-talks between microRNAs and mRNAs in pancreatic tissues of streptozotocin-induced type 1 diabetic mice

Abstract

Abstract. Network cross-talks between microRNAs (miRNAs) and mRNAs may be useful to elucidate the pathological mechanisms of pancreatic islet cells in diabetic individuals. The aim of the present study was to investigate the cross-talks between miRNAs and mRNAs in pancreatic tissues of streptozotocin-induced diabetic mice through microarray and bioinformatic methods. Based on the miRNA microarray, 64 upregulated and 72 downregulated miRNAs were observed in pancreatic tissues in diabetic mice compared to the normal controls. Based on the mRNA microarrray, 507 upregulated mRNAs and 570 downregulated mRNAs were identified in pancreatic tissues in diabetic mice compared to the normal controls. Notably, there were 246 binding points between upregulated miRNA and downregulated mRNAs; simultaneously, there were 583 binding points between downregulated miRNA and upregulated mRNAs. These changed mRNA may potentially involve the following signaling pathways: Insulin secretion, pancreatic secretion, mammalian target of rapamycin signaling pathway, forkhead box O signaling pathway and phosphatidylinositol 3-kinase-protein kinase B signaling. The fluctuating effects of miRNAs and matched mRNAs indicated that miRNAs may have wide cross-talks with mRNAs in pancreatic tissues of type 1 diabetic mice. The cross-talks may play important roles in contributing to impaired islet functions and the development of diabetes. However, further functional validation should be conducted in the future. IntroductionDiabetes mellitus is a complex metabolic disease demonstrating impaired islet function (1,2). Destruction of β-cells or the failure of these insulin-secreting cells to compensate for increased metabolic demand may account for the development of diabetes. Apoptosis, oxidative stress, mitochondrial dysfunction and endoplasmic reticulum (ER) stress responses, including c-Jun N-terminal kinase (JNK) activation, have been suggested as mechanisms for the changes of pancreatic β-cells in type 2 diabetes mellitus (T2DM) (3). T1DM is the result of autoimmune destruction of pancreatic β cells (4). However, the mechanisms involved in islet dysfunction remain unclear. microRNAs (miRNAs) play a key role in regulating islet function (5). Repression of mRNAs by miRNAs is an important mechanism for regulation of expression during cell fate specification, apoptosis and metabolism (6). In the previous study, miRNA-mRNA interactions were investigated in the pancreatic islets of spontaneously diabetic Goto-Kakizaki rats (7) and the human pluripotent stem cells based in vitro model of pancreatic differentiation (8). A number of key pairs of miRNA-mRNA were proposed to have significant roles in the pathogenesis of T2DM or islet development. However, few studies have reported the miRNA-mRNA cross-talk in T1DM.In the present study, the cross-talks between miRNAs and mRNAs in the streptozotocin (STZ)-induced T1DM mice were investigated. Materials and methodsEstablishment of T1DM mouse model. Male National Institutes of Health (NIH) mice (age, 4 weeks) were...

Dysregulated Circulating micro RNAs Markers: New Evidence into Expression Pattern in Children with T1D among Egyptian Population

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MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatic analysis

“…1 . According to the search criteria, a total of 1738 publications were retrieved from databases; however, after full text analysis, only 33 articles ( 20 , 22 , 23 , 24 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ) fulfilled the eligibility criteria and were included in the review. The main characteristics of these 33 articles are shown in Table 1 .…”

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