Long non-coding RNAs: The hidden players in diabetes mellitus-related complications

Abstract

Background and aim: Long non-coding RNAs (lncRNAs) have been recognized as important regulators of gene expression in various human diseases. Diabetes mellitus (DM) is a long-term metabolic disorder associated with serious macro and microvascular complications. This review discusses the potential lncRNAs involved in DM-related complications such as dysfunction of pancreatic beta islets, nephropathy, retinopathy, cardiomyopathy, and peripheral neuropathy.

Methods: An extensive literature search was conducted in the Scopus database to find information from reputed biomedical articles published on lncRNAs and diabetic complications from 2014 to 2023. All review articles were collected and statistically analyzed, and the findings were summarized. In addition, the potential lncRNAs involved in DM-related complications, molecular mechanisms, and gene targets were discussed in detail.

Results: The lncRNAs ANRIL, E33, MALAT1, PVT1, Erbb4-IR, Gm4419, Gm5524, MIAT, MEG3, KNCQ1OT1, Uc.48+, BC168687, HOTAIR, and NONRATT021972 were upregulated in several diabetic complications. However, βlinc1, H19, PLUTO, MEG3, GAS5, uc.322, HOTAIR, MIAT, TUG1, CASC2, CYP4B1-PS1-001, SOX2OT, and Crnde were downregulated. Remarkably, lncRNAs MALAT1, ANRIL, MIAT, MEG3, H19, and HOTAIR were overlapping in more than one diabetic complication and were considered potential lncRNAs.

Conclusion: Several lncRNAs are identified as regulators of DM-related complications. The expression of lncRNAs is up or downregulated depending on the disease context, target genes, and regulatory partners. However, most lncRNAs target oxidative stress, inflammation, apoptosis, fibrosis, and angiogenesis pathways to mediate their protective/pathogenic mechanism of action and contribute to DM-related complications.

Keywords: Complications; LncRNA; diabetic; hyperglycemia; ncRNA.