Potential Diagnostic Biomarkers of tRNA-Derived Small RNAs in PBMCs for Nonproliferative Diabetic Retinopathy in Patients With Type 2 Diabetes Mellitus.

Purpose: This study aimed to reveal the altered expressions of transfer RNA (tRNA)-derived small RNAs (tsRNAs) in peripheral blood mononuclear cells and identify potential diagnostic biomarkers for nonproliferative diabetic retinopathy (NPDR) from patients with type 2 diabetes mellitus.

Methods: Fifty-three patients diagnosed with type 2 diabetes mellitus were enrolled, including 25 patients with NPDR and 28 patients without diabetic retinopathy (DR) as the control group. A small RNA microarray was performed to screen the differentially expressed tsRNAs. Reverse transcriptase quantitative polymerase chain reaction was used to validate the significantly altered tsRNAs in a screening cohort and a verification cohort. The target genes, their enriched functions, and signaling pathways were predicted by bioinformatics analyses.

Results: In total, 668 upregulated and 485 downregulated tsRNAs were found in the NPDR group by microarray. Eight tsRNAs were validated preliminarily to be altered significantly by reverse transcriptase quantitative polymerase chain reaction, and their target genes were enriched in cellular macromolecule metabolic process and ubiquitin-mediated proteolysis. The verification experiments confirmed the increased levels of 5'tiRNA-35-PheGAA-8, tRF3-28-PheGAA-1, and tRF3b-PheGAA-6, and the decreased levels of mt-tRF3-19-ArgTCG, mt-tRF3-20-ArgTCG, and mt-tRF3-21-ArgTCG in patients with NPDR, which may serve as potential biomarkers with clinical significance.

Conclusions: The study recognized the tsRNA expression changes in peripheral blood mononuclear cells from patients with NPDR and discovered potential diagnostic biomarkers that hold clinical significance.

Translational Relevance: The significantly altered tsRNAs identified in the study may serve as potential diagnostic biomarkers for patients with NPDR as well as possible molecular targets of the occurrence and development of DR.