Exosomal miRNAs and isomiRs: potential biomarkers for type 2 diabetes mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is a metabolic disease that is characterized by chronic hyperglycaemia. MicroRNAs (miRNAs) are single-stranded, small non-coding RNAs that play important roles in post-transcriptional gene regulation. They are negative regulators of their target messenger RNAs (mRNAs), in which they bind either to inhibit mRNA translation, or to induce mRNA decay. Similar to proteins, miRNAs exist in different isoforms (isomiRs). miRNAs and isomiRs are selectively loaded into small extracellular vesicles, such as the exosomes, to protect them from RNase degradation. In T2DM, exosomal miRNAs produced by different cell types are transported among the primary sites of insulin action. These interorgan crosstalk regulate various T2DM-associated pathways such as adipocyte inflammation, insulin signalling, and β cells dysfunction among many others. In this review, we first focus on the mechanism of exosome biogenesis, followed by miRNA biogenesis and isomiR formation. Next, we discuss the roles of exosomal miRNAs and isomiRs in the development of T2DM and provide evidence from clinical studies to support their potential roles as T2DM biomarkers. Lastly, we highlight the use of exosomal miRNAs and isomiRs in personalized medicine, as well as addressing the current challenges and future opportunities in this field. This review summarizes how research on exosomal miRNAs and isomiRs has developed from the very basic to clinical applications, with the goal of advancing towards the era of personalized medicine.

Keywords

extracellular vesicles / insulin resistance / hyperglycaemia / obesity / precision medicine

Acknowledgements

This work is funded by the Malaysia Ministry of Science, Technology, and Innovation (MOSTI) (Grant No. RD0120Q1410) awarded to YFP and WR, and the postgraduate student scholarships awarded by the University of Nottingham Malaysia to YLS.

Authors’ contributions

YLS and YFP made substantial contributions to the conceptualization of the paper. YLS drafted the manuscript and figures. YFP, WMC, WR, and YP provided supervision support. YFP and WR involved in funding acquisition. WMC, WR, SMZ, SZSAK, YP, and YFP reviewed and edited the manuscript. All authors gave their approval of the version to be published.

Conflict of interests

All authors declared that there are no conflict of interests.

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