Gene expression profiles and possible interactions between microRNAs and mRNAs in type 1 Diabetes Mellitus, focusing on response to oxidative stress and DNA repair

Abstract

Diabetes mellitus affects over 165 million people worldwide and it is a group of diseases characterized by extracellular chronic hyperglycemia. The latter is a consequence of the deficiency of insulin action and this hormone in turn, is responsible for regulating physiological glucose blood levels. The present study focuses on type 1 diabetes mellitus (T1D), one of the categories of diabetes. This type of diabetes results from an autoimmune process in which the insulin-producing ² cells are eliminated, leading to insulin deficiency; and for this reason, patients affected by T1D are insulin-dependent. They also comprise approximately 10% of the diabetic patients and the great majority of them are children. One of the consequences of hyperglycemia is the increase in the levels of reactive oxygen species (ROS), which can cause DNA damage. Base excision repair (BER) is the major mechanism involved in the repair of oxidative DNA damage, although nucleotide excision repair (NER) and mismatch repair (MMR) have also been implicated. A number of studies have associated the regulation of genes involved in the DNA repair with microRNAs (RNAs composed of 20-25 nucleotides that do not encode any protein but play a role in the negative regulation of many cellular processes). Hence, the present study focuses on investigating the association between T1D and the regulation of genes involved in the oxidative DNA damage repair by microRNAs. In order to accomplish that, we will study the expression profile of microRNAs (by microarrays) and both the gene and protein expression of potential targets of these microRNAs that are implicated in the DNA repair (that will be obtained from the microarray method and whose expression will be confirmed by qPCR) in T1D patients compared to normal subjects (control group).