The Multifaceted Roles of LncRNAs in Diabetic Complications: A Promising Yet Perplexing Paradigm

As the global epidemic of diabetes continues to grow at an alarming rate, the risk for developing diabetes-associated comorbidities will remain at an all-time high. Diabetic complications, which are separated into macro- and microvascular complications, are not only debilitating for the patient, but these chronic complications also pose significant treatment challenges for healthcare providers. In order to reduce the burden of diabetes and expand the clinical armamentarium for diagnosis and treatment, better understanding of the molecular mechanisms underlying the pathogenesis of diabetic complications becomes fundamental. Previously, a growing body of evidence has documented key cellular events that contribute to the progression of diabetic complications: angiogenesis, fibrosis, inflammation, and oxidative stress. However, in the last decade, recent advances in genomic technology have identified several novel epigenetic alterations that are also implicated in the progression of diabetes and its complications—alluding to the complex nature of this disease. Among these epigenetic processes, long noncoding RNAs (lncRNAs) are key regulators that are involved in altering gene expression without modifying the underlying nucleotide composition of the genome. Despite possessing no protein-coding potential and being greater than 200 nucleotides in length, lncRNAs can alter chromatin configuration by interacting with several enzymes that facilitate chromatin remodeling and gene regulation. In this chapter, we will provide a comprehensive overview of the well-documented lncRNAs that are known to impact the key cellular events implicated in the progression of diabetic complications.