Is mirna-30d-5p an appropriate biomarker for type 2 diabetes?

Taravat Ghane roudbaraki,1 Vahide hasanzade,2,* Naeime roshanzamir,3

1. University of Tehran
2. University of Tehran
3. University of Tehran

Abstract

Introduction

Diabetes mellitus (dm) is a global health problem which affects ~450 million individuals worldwide. patients with diabetes mellitus develop serious complications that reduce their quality of life and life expectancy if the disease is not diagnosed at an early onset. biomarkers for early detection of the disease, distinction of different subtypes of diabetes and identification of individuals at risk of developing complications would greatly improve the disease diagnosis and patients care. looking for a new biomarker that is likely to respond to this medical need, one highly suitable source is represented by micrornas (mirnas). mirnas are released by most cells in the body, reach blood circulation in a very stable form and may be used to assess cell activity at distance. they enter the bloodstream encircled by membranous vesicles (exosomes and microparticles), lipoproteins, and other ribonucleoprotein complexes. one of the major problems in the study of diabetic patients is the lack of a suitable biomarker associated with β-cell destruction. perhaps circulating islet-specific mirnas are a good biomarker to diagnose the function of β-cells in various types of diabetes. according to previous studies, mir-30d-5p is one of mirnas up-regulated by glucose in the pancreatic β-cell. overexpression of mir-30d-5p increased insulin gene expression, while inhibition of mir-30d-5p abolished glucose-stimulated insulin expression. findings indicate that overexpression of mir-30d-5p is associated with increase in the expression of a specific β-cell transcription factor called mafa. on the other hand, wang et al found that mir-30d-5p could enhance islet β-cell function, promote proliferation, and inhibit cell apoptosis by targeting socs3 through the suppression of the jnk signaling pathway. in this review, we focus on studies considering circulating mir-30d-5p as biomarkers of diabetic complications.

Methods

The first study reporting dysregulation of circulating microrna in diabetic patients was published in 2010. thus, we reviewed the articles published on this issue from 2010 onwards using the following keywords:‘mir-30d-5p’, ‘diabetes’ ‘expression’ ‘profile’ ‘profiling’.. eligible studies had to meet the inclusion criteria: (1) they were mirna expression profiling studies on patients with diabetes; (2) they used diabetic and non-diabetic control samples for comparison; (3) they reported significant dysregulation of hsa-mir-30d-5p expression in diabetic patients.

Results

The main findings on this subject come from four important studies. kong et al detected an increase in the expression of mir‑30d-5p and six other diabetes-related mirnas in plasma of patients with type 2 diabetes (t2d) compared with pre-diabetic patients however, there was no change in mir‑30d-5p expression between pre-diabetic and healthy subjects. in a concurrent study, karolina et al analyzed eight mirnas in whole blood of pre-diabetic and type 2 diabetic patients and found that all eight tested mirnas were differentially expressed. unlike the previous study, they reported a decrease in the expression of mir-30d-5p. seyhan et al compared plasma expression levels of a panel of 28 mirnas associated with islet function or previously associated with diabetes in subjects with pre-diabetes and t2d to those of healthy controls. they reported that mir-30d and mir-34a were most significantly increased in type 2 diabetic patients relative to healthy controls. finally, in a study conducted in 2017, candia et al found that the level of mir-30d-5p is decreased in pre-diabetic subject compared to healthy or diabetic individuals.

Conclusion

These studies indicate that increased level of circulating mir-30d-5p in the bloodstream is specific to t2d. therefore, it seems that circulating mir-30d-5p is a good biomarker for the diagnosis of type 2 diabetes. furthermore, given that the level of circulating mir-30d-5p in pre-diabetic subjects was reduced compared with diabetic and control subjects, this microrna could be used for early diagnosis of type 2 diabetes. however, coherent results are still scarce. this could be due to differences in source sample, population ethnicity, pre-analytical and analytical procedures, microrna quantification platforms and data normalization processes.

Keywords

Diabetes, biomarker, mirna-30d-5p, expression