Abstract
Background: Diabetic retinopathy (DR) is a common diabetes complication and was considered as the major cause of blindness among young adults. MiRNAs are a group of small non-coding RNAs regulating the expression of target genes and have been reported to be associated with the development of DR in a variety of molecular mechanisms. In this study, we aimed to identify miRNAs that are differentially expressed (DE) in the serum of DR patients.Methods: We recruited 21 type 2 diabetes mellitus (T2DM) inpatients of Chinese Han ancestry, consisting of 10 non-proliferative DR patients (DR group) and 11 non-DR T2DM patients (NDR group). MiRNA was extracted from fasting peripheral serum and quantified by RNA-seq. The expression levels of miRNA were evaluated and compared between the two groups, with adjustments made for age differences. The validated target genes of miRNAs were subjected to a pathway analysis. We also constructed a weighted polygenic risk score using the DE miRNA and evaluated its predictive power.Results: Five miRNAs were DE between DR and NDR groups (p-Value ≤ 0.01, LFC ≥ 2 or LFC ≤-2). These included miR-4448, miR-338-3p, miR-190a-5p, miR-485-5p, and miR-9-5p. In total, these miRNAs were validated to regulate 55 target genes. Four target genes were found to overlap with the NAD metabolism, sirtuin, and aging pathway, which was thought to control the vascular growth and morphogenesis. The predictive power of our polygenic risk score was apparently high (AUC = 0.909). However, it needs to be interpreted with caution.Conclusion: In this study, we discovered novel DR-specific miRNAs in human serum samples. These circulating miRNAs may represent the pathological changes in the retina in response to diabetes and may serve as non-invasive biomarkers for early DR risk prediction.
Highlights
Diabetic retinopathy (DR) is one of the most common and serious complications in diabetes and considered as the leading cause of blindness in adults (Zhang et al, 2018)
Our goal in this study is to identify miRNAs that are differentially expressed (DE) in DR patients, and further investigate whether circulating miRNAs can be used as biomarkers in predicting the DR onset in type 2 diabetes mellitus (T2DM) patients
Twenty-one T2DM patients were included in our study
Summary
Diabetic retinopathy (DR) is one of the most common and serious complications in diabetes and considered as the leading cause of blindness in adults (Zhang et al, 2018). MiRNAs have been noted to be very stable in a variety of body fluids, such as serum, plasma, saliva, tears, aqueous and vitreous humor, and urine (Ye and Steinle, 2017; Shaker et al, 2018) In addition to their regulatory functions of gene expression and as a potential therapeutic target, miRNA is considered as a useful and accessible diagnostic marker for many diseases, including non-small-cell lung cancer (Shao et al, 2017), breast cancer (Li et al, 2016), gastric cancer (Pereira et al, 2019), coronary artery disease (Zhang et al, 2019), as well as a potential mediator of physiological and pathological processes (Ye and Steinle, 2017). We aimed to identify miRNAs that are differentially expressed (DE) in the serum of DR patients
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