Current insights and advances in long noncoding RNA dysregulation in diabetes and its complications

Long noncoding RNAs (lncRNAs) are pivotal regulators in the pathophysiology of diabetes mellitus and its complications, including diabetic retinopathy, nephropathy, and cardiomyopathy. They influence essential cellular processes such as angiogenesis, vascular smooth muscle cell behavior, inflammation, extracellular matrix remodeling, and apoptosis. In cardiomyopathy, lncRNA H19 promotes cardiomyocyte survival by regulating autophagy, highlighting its role in cardiovascular outcomes. In addition, lncRNAs hold promise as noninvasive biomarkers, detectable in extracellular fluids such as serum and urine, providing novel diagnostic tools. For example, elevated levels of HOX transcript antisense RNA and promoter of CDKN1A antisense DNA damage-activated RNA correlate with hyperglycemia and its complications, whereas maternally expressed gene 3 and metastasis-associated lung adenocarcinoma transcript 1 are linked to insulin resistance. However, the full scope of lncRNA mechanisms and therapeutic potential remains unclear. Recent research emphasizes the importance of studying the molecular pathways influenced by lncRNAs, such as the Janus kinase/signal transducer and activator of transcription and p38 mitogen-activated protein kinase pathways, which regulate inflammation and insulin signaling. Preclinical studies show promising outcomes for lncRNA-targeted therapies; however, challenges remain in precise detection and delivery. Addressing these gaps through advanced RNA sequencing and targeted therapies is crucial for developing lncRNA-based diagnostics and treatments for diabetes complications. This review explores lncRNAs as biomarkers and therapeutic targets, focusing on their regulatory mechanisms in diabetic complications such as retinopathy, nephropathy, and cardiomyopathy.