Expression profile of tRNA‑derived fragments and their potential roles in human varicose veins.

Abstract

Varicose veins (VVs) is a common disease presenting with chronic venous insufficiency. tRNA-derived fragments (tRFs) are associated with a variety of pathological conditions. However, the functions of tRFs in VVs have not been elucidated to date. The present study aimed to identify the key tRFs and investigate their potential roles in VVs. Small RNA sequencing (RNA-seq) was performed to investigate the expression of tRFs in tissues of patients with VVs and their matched adjacent normal veins tissues (ANVs). Reverse transcription-quantitative PCR (RT-qPCR) was used to confirm the differential expression of tRFs. A total of 13,789 tRFs were identified by small RNA-seq, including 45 differentially expressed tRFs (DETs), which comprised 14 upregulated and 31 downregulated tRFs in VV tissues compared with ANVs. In addition, DETs were mainly involved in the function of epidermal growth factor receptor and vascular endothelial growth factor receptor signaling pathways in VVs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target genes of DETs were predominantly involved in Wnt and mitogen-activated protein kinase (MAPK) signaling pathways, as well as calcium signaling. Additionally, two upregulated tRFs (tRF-36-F900BY4D84KRIME and tRF-23-87R8WP9IY) and one downregulated tRF (tRF-40-86J8WPMN1E8Y7Z2R) were further validated by RT-qPCR, and a signaling pathway regulation network of their target genes confirmed their involvement in the calcium, Wnt and MAPK signaling pathways. The results of the present study identified three DETs (tRF-36-F900BY4D84KRIME, tRF-23-87R8WP9IY and tRF-40-86J8WPMN1E8Y7Z2R), which may have crucial roles in the occurrence and progression of VVs by regulating Wnt and MAPK signaling, as well as calcium signaling. The present results may provide a basis for further investigation of the functional roles of tRFs in VVs.