Discovery and validation of hsa_circ_0001953 as a potential biomarker for proliferative diabetic retinopathy in human blood

Abstract

This study aimed to determine whether circular RNAs (circRNAs) in whole blood could be served as novel non-invasive biomarkers for proliferative diabetic retinopathy (PDR). Methods: This retrospective cross-sectional study comprised 34 healthy participants, 34 PDR patients and 34 non-proliferative DR (NPDR) patients. Highthroughput whole transcriptome sequencing was performed to explore the expression profile of circRNAs in the whole blood, and the candidate circRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). Receiver operating characteristic (ROC) analysis evaluated the ability of these candidate circRNAs in discriminating PDR patients from NPDR patients and healthy subjects. Finally, the networks of circRNA-miRNA-mRNA based on the candidate circRNAs were constructed. Results: Using sequencing and qRT-PCR, hsa_circ_0001953 was found to be elevated in PDR patients in contrast with the other two groups. Statistical analysis showed that the expression levels of hsa_circ_0001953 in PDR patients were positively related to the duration of diabetes and HbAc1. Receiver operating characteristic (ROC) curve analysis revealed that hsa_circ_0001953 was associated with a high diagnostic accuracy in discriminating PDR patients from NPDR patients and healthy controls, resulting in an area under the curve (AUC) of 0.87 and 0.92, respectively. The circRNA-miRNA-target gene networks for hsa_circ_0001953 showed that hsa_circ_0001953 could interact with dozens of miRNAs and some targeted mRNAs have been potentially involved in the pathogenesis of diabetes. Conclusion:The present findings indicate that hsa_circ_0001953 in the whole blood may serve as a novel diagnostic biomarker and potential therapeutic target for PDR.

Circular RNAs in diabetes and its complications: Current knowledge and future prospects

“…In terms of proliferative DR, circRNA could serve as a diagnostic biomarker. Zhang et al ( Wu et al, 2021a ) reported that hsa_circ_0001953 levels were increased in the blood of proliferative DR patients compared with healthy participants and non-proliferative DR patients. However, it needs to verify in a large population.…”

Circular RNAs in diabetes mellitus and its complications

“…The levels of seven circRNAs, including hsa_circRNA_063981, hsa_circRNA_404457, hsa_circRNA_100750, hsa_circRNA_406918, hsa_circRNA_104387, hsa_circRNA_103410, and hsa_circRNA_100192, are distinctly increased in the serum of T2DM patients with PDR ( 75 ), implying a potential role of circRNAs as biomarkers for DR. Additionally, hsa_circ_0001953 was reported to be increased in the blood of PDR patients and is positively correlated with the duration of DM and hemoglobin A1c levels. This study indicated a potential value of hsa_circ_0001953 in distinguishing PDR patients from NPDR patients and healthy controls ( 76 ).…”

Circ_001209 aggravates diabetic retinal vascular dysfunction through regulating miR-15b-5p/COL12A1

“…As a new type of non-coding RNA, circRNAs have closed-loop structure and are widely involved in cell proliferation, differentiation, apoptosis and other different cellular physiological or pathological processes [ 27 ]. Recent studies [ 28 ] have found that abnormal expression of circRNAs may be involved in pathological processes such as inflammation and vascular dysfunction in diabetic retinopathy by sponging microRNAs. Zou et al [ 29 ] suggested that circRNA COL1A2 promoted angiogenesis by regulating the miR-29b/VEGF axis and aggravated the damage of diabetic retinopathy.…”