Systematic and integrated analysis of tRNA-derived small RNAs reveals novel potential pathogenesis targets of sarcoidosis

Abstract

Abstract The pathogenesis of sarcoidosis, which involves several systems, is unclear, and its pathological type is non-caseating epithelioid granulomas. tRNA-derived small RNA (tsRNA) is a novel class of short non-coding RNAs with potential regulatory functions. However, whether tsRNA contributes to sarcoidosis pathogenesis remains unclear. Deep sequencing technology was used to identify alterations in tsRNA expression profiles between patients with sarcoidosis and healthy controls. A total of 360 tsRNAs were identified for exact matches. Among them, the expression of three tRNAs (tiRNA-Glu-TTC-001, tiRNA-Lys-CTT-003, and tRF-Ser-TGA-007) was markedly regulated in sarcoidosis and validated by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of various tsRNAs was significantly correlated with age, the number of affected systems, and calcium levels in the blood. Additionally, target prediction and bioinformatics analyses revealed that these tsRNAs may play roles in chemokine, cAMP, cGMP-PKG, retrograde endorphin, and FoxO signalling pathways. The Cytoscape software was used for visual analysis to obtain 10 hub genes of each target tsRNA. Among the hub genes, APP, PRKACB, ARRB2, and NR5A1 finding may participate in the occurrence and development of sarcoidosis through immune inflammation. This study provides novel insights to explore tsRNA as a novel and efficacious pathogenic target of sarcoidosis.