Roles of miRNAs and long noncoding RNAs in the progression of diabetic retinopathy

Abstract

Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults across the world. The pathogenesis of DR is multifactorial and the molecular mechanisms are still not fully understood. Accumulating evidence has demonstrated that noncoding RNAs (ncRNAs) may be aberrantly expressed and may play vital roles in the development of DR. Amongst ncRNAs, miRNAs and long ncRNAs (lncRNAs) are known for their regulatory functions. Here, we summarize the functions and mechanisms of known aberrantly expressed miRNAs and lncRNAs in DR. Additionally, a novel lncRNA–mRNA–miRNA network is included in this review. We highlight original studies that provide detailed data about the mechanisms of miRNAs and lncRNAs, their applications as diagnostic or prognostic biomarkers, and their potential therapeutic targets. In conclusion, this review will help us gain a better understanding of the molecular mechanisms by which miRNAs and lncRNAs perform their functions in DR, and provide general strategies and directions for future research.

Transthyretin Upregulates Long Non-Coding RNA MEG3 by Affecting PABPC1 in Diabetic Retinopathy

“…As previously reported, lncRNAs could competitively bind common miRNAs as ceRNAs [25,37,38] and regulate miR-223-3p expression by lncRNA-MEG3, which has been observed in other diseases [30].…”

“…Still, the regulatory mechanisms involving TTR in DR are not entirely clear.Long non-coding RNAs (lncRNAs) regulate targeted mRNA expression via the microRNA (miRNA) response element known as competing endogenous RNA (ceRNA) [18,19]. LncRNAs are known to play vital roles in ocular disease [20], including glaucoma [21,22], retinoblastoma [23,24], and DR [25,26]. Recently, the study of lncRNAs in DR has become a hot point.…”

Dyslipidemia in retinal metabolic disorders

“…The function of MRPL19 is unclear but other MRP genes including MRPL9 and MRPL23 are associated with retinitis pigmentosa (Kenmochi et al, 2001). Increasing evidence suggests a potential role of noncoding RNAs in regulating retinal inflammation during DR development (Gong & Su, 2017).…”

Plasma levels of miR‐29b and miR‐200b in type 2 diabetic retinopathy

“…In this context, several studies have reported abnormal expression of microRNAs (miRNAs/miRs) in retinal cells under hyperglycemic conditions and in murine models of DR . MiRNAs are small endogenous non‐coding RNAs that in general silence gene expression at the posttranscriptional level by pairing to specific sequences in the 3’‐untranslated region of their target mRNAs, thereby repressing protein synthesis.…”

“…1,4 Epigenetic mechanisms, such as DNA methylation, histone post-translational modifications in chromatin and non-coding RNAs, mediate the interplay between genetic and environmental risk factors. Persistence of epigenetic changes might contribute to the metabolic memory phenomenon and to the oxidative stress, inflammation and extracellular matrix accumulation, 5,6 all of which lead to the development of DR. 5 In this context, several studies have reported abnormal expression of microRNAs (miRNAs/miRs) in retinal cells under hyperglycemic conditions and in murine models of DR. [7][8][9] MiRNAs are small endogenous non-coding RNAs that in general silence gene expression at the posttranscriptional level by pairing to specific sequences in the 3'-untranslated region of their target mRNAs, thereby repressing protein synthesis. MiRNAs regulate cell development and function by modulating the acquisition and maintenance of beta-cell identity, 10 cell growth, proliferation, differentiation, apoptosis and metabolism.…”