Abstract
Aims. Noncoding RNAs (ncRNAs) play an important role in the occurrence and development of type 2 diabetes mellitus (T2DM). This paper summarized the current evidences of the involvement microRNAs, long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) in the differential expressions and their interaction with each other in T2DM. Methods. The differentially expressed miRNAs, lncRNAs, and circRNAs in the blood circulation (plasma, serum, whole blood, and peripheral blood mononuclear cells) of patients with T2DM were found in PubMed, GCBI, and other databases. The interactions between ncRNAs were predicted based on the MiRWalk and the DIANA Tools databases. The indirect and direct target genes of lncRNAs and circRNAs were predicted based on the starBase V2.0, DIANA Tools, and LncRNA-Target databases. Then, GO and KEGG analysis on all miRNA, lncRNA, and circRNA target genes was performed using the mirPath and Cluster Profile software package in R language. The lncRNA–miRNA and circRNA–miRNA interaction diagram was constructed with Cytoscape. The aim of this investigation was to construct a mechanism diagram of lncRNA involved in the regulation of target genes on insulin signaling pathways and AGE–RAGE signaling pathways of diabetic complications. Results. A total of 317 RNAs, 283 miRNAs, and 20 lncRNAs and circRNAs were found in the circulation of T2DM. Dysregulated microRNAs and lncRNAs were found to be involved in signals related to metabolic disturbances, insulin signaling, and AGE–RAGE signaling in T2DM. In addition, lncRNAs participate in the regulation of key genes in the insulin signaling and AGE–RAGE signaling pathways through microRNAs, which leads to insulin resistance and diabetic vascular complications. Conclusion. Noncoding RNAs participate in the occurrence and development of type 2 diabetes and lead to its vascular complications by regulating different signaling pathways.
Highlights
Epidemiological investigation showed that there are approximately 422 million diabetes patients worldwide at present, which is estimated to rise up to 642 million in the global population by 2040 [1]
A total of 9,923 articles were retrieved in a search of several online databases, and 4,179 remaining articles resulted from a screening of the Materials and Methods to eliminate duplicates, 2,549 of which were not relevant
This study found that eight long noncoding RNAs (lncRNAs) can participate in insulin signal transduction by regulating 17 miRNAs (Figure 6)
Summary
Epidemiological investigation showed that there are approximately 422 million diabetes patients worldwide at present, which is estimated to rise up to 642 million in the global population by 2040 [1]. More than 90% are with type 2 diabetes mellitus (T2DM), and the trend has been toward a younger population lately [2]. The current trends have made its prevention necessary. Genes and lifestyle could both trigger T2DM with hyperglycemia [3]. Serious complications, such as diabetic, cardiovascular, and cerebrovascular diseases, and diabetic retinopathy, which are the main reasons for deaths among T2DM patients, can be caused by uncontrolled hyperglycemia and could increase the risk of cancer [4,5,6,7]. The prevention and treatment of diabetes is a long-term challenge
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