MALAT1 as a Diagnostic and Therapeutic Target in Diabetes-Related Complications: A Promising Long-Noncoding RNA

Abstract

Diabetes mellitus is a global issue with increasing incidence rate worldwide. In an uncontrolled case, it can advance to various organ-related complications leading to an increase in morbidity and mortality. Long non-coding RNA (lncRNA) Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appears to be a fairly novel lncRNA that is relevant to diabetes and its role in diabetic-related diseases initiation and progression have long been a subject of attention to many scholars. The expression of MALAT1 is elevated in different diabetic-related diseases. In this review, we demonstrate the various functions of MALAT1 in the different diabetes-related complications including ischemic reperfusion injury, retinopathy, cataract, atherosclerosis, cardiomyopathy, non-alcoholic steatohepatitis, gastroparesis, kidney disease, and gestational diabetes. The emerging evidence showed that the role of MALAT1 in diabetic-related complications is both pro-inflammatory and apoptosis in different cell types. These results concluded that MALAT1 is a potential diagnostic and future targeted therapy for diabetes-associated complications.

Keywords: MALAT1; diabetes mellitus; diabetes-related complications; long non-coding RNA.

Figure 1

Various regulatory mechanisms of MALAT1 in different diabetes-related complications. (A) Hyperglycaemia-induced MALAT1 trigger an inflammatory response in microglial cells via activation of MyD88 signalling leading to ischemic reperfusion injury. (B) MALAT1 recruits PRC2 to bind anti-inflammatory gene promoter which suppresses its transcription and subsequently increases inflammatory response leading to retinopathy. (C) Hyperglycaemia induces Sp1 protein binding to the MALAT1 promoter gene increasing MALAT1 expression, increased MALAT1 activates p38MAPK pathway causing apoptosis and oxidative stress leading to cataract formation. (D) MALAT1 inhibits miR-23 which in turn increases ELAVL1 and NLRP3 leading to atherosclerosis. (E) Hyperglycaemia promotes MALAT1 levels which trigger inflammatory cytokines TNF-α, IL-1β and IL-6 leading to inflammation and cardiomyopathy. (F) MALAT1 promotes cxcl5 chemokine via cxcl5 gene transcript which triggers inflammation, fibrosis and NASH. (G) MALAT1 decreases α-SMA, SM myosin heavy chain diminishes contractility leading to gastroparesis. (H) MALAT1 antagonized the effect of miR-23 on its target ELAVL1, NLRP3 promoting pyroptosis and diabetic nephropathy.