Exosomal tRF-Leu-AAG-001 derived from mast cell as a potential non-invasive diagnostic biomarker for endometriosis

Abstract

Background The diagnosis of endometriosis (EMs) is still based on laparoscopic observation. This study tries to verify whether exosomal tRNA-derived fragments (tRFs) in leucorrhea can be used as non-invasive diagnostic markers. Methods Endometrial tissues and leucorrhea were sampled from women hospitalized in Ningbo University Affiliated Hospital from January 2021 to July 2021 with (n = 26) and without endometriosis (n = 25). Exosomes were isolated from samples by differential centrifugation. The small RNA sequencing was performed to detect the exosomal tRNA halves (tiRNAs)&tRFs. RNA probe and immunofluorescence antibody were used to localize the origin of tRFs. From mast cell lines infected with tRF-Leu-AAG-001 siRNA, we observed the change in vascular capacity and expression of inflammatory factors. The specificity and sensitivity tRF were determined by receiver operating characteristic analyses. Results 63 up-regulated and 45 down-regulated tRFs&tiRNAs were identified in ectopic exosomes. We selected tRF-Leu-AAG-001 as a candidate marker through KEGG pathway enrichment and PCR verification. We found that mast cells highly expressed tRF-Leu-AAG-001 in ectopic foci by immunofluorescence staining. We used siRNA to silenced tRF-Leu-AAG-001 expression in luva, qPCR analysis showed IL-6, IL-10, IL-1β, and TNF-α were significantly decreased. Meanwhile, tRF-Leu-AAG-001 siRNA dramatically reduced the angiogenic ability of luva. Finally, we examined the expression of exosomal tRF-Leu-AAG-001 in the leucorrhea. It was found exosomal tRF-Leu-AAG-001 had high specificity and sensitivity for predicting the occurrence of ectopic disease. Conclusions Exosomal tRF-Leu-AAG-001 derived from mast cells in ectopic foci might promote inflammation and angiogenesis. Meanwhile, leucorrhea exosomal tRF-Leu-AAG-001 could be a potential diagnostic biomarker for endometriosis.

Ushering in the era of tRNA medicines

“…( 52 ) analyzed tRFs in blood samples and identified 11 differentially expressed molecules with prognostic value for non–small cell lung cancer. Other studies expanded the potential of tRF-based diagnostics in liver ( 53 ), gastric ( 54 ) and colorectal cancers ( 55 ), as well as in disorders as diverse as autoimmune nephritis ( 56 ), Parkinson’s disease ( 57 ), endometriosis ( 58 ), and osteoporosis ( 59 ).…”

M1 macrophage-derived extracellular vesicle containing tsRNA-5006c promotes osteogenic differentiation of aortic valve interstitial cells through regulating mitophagy

“…For example, Zhang et al revealed that plasma exosomal tRF-25-R9ODMJ6B26, tRF-38-QB1MK8YUBS68BFD2, and tRF-18-BS68BFD2 might be diagnostic biomarkers for osteoporosis detection ( Zhang et al, 2018 ). Mast cell-derived exosomal tRF-Leu-AAG-001 may have a promotion function in inflammation and angiogenesis and leucorrhea exosomal tRF-Leu-AAG-001 might be diagnostic biomarkers for endometriosis ( Li et al, 2022 ). Alveolar macrophage-derived exosomal tRF-22-8BWS7K092 could prompt acute lung injury through the ferroptosis pathway ( Wang et al, 2022b ).…”

Extracellular vesicles in endometriosis: role and potential

“…At least 1449 mRNAs, 938 lncRNAs, 39 miRNAs, and 61 competing endogenous RNAs (ceRNAs) were identified to display differential expression patterns in EVs derived from endometrial stromal cells (ESCs) of patients without EMs compared to ESCs of patients with EMs, including ESCs from ovarian endometrioma and those from eutopic endometrium (27). Another study found 63 up-regulated and 45 down-regulated tiRNAs and tRFs in ectopic tissue EVs from EMs (28). It was also found that lncRNAs MEG8, SNHG25, LINC00293 and RP5-898J17.1 were down-regulated, while lncRNAs LINC00998, PVT1, and RP4-561L24.3 were significantly up-regulated in ectopically diseased EVs from EMs patients (29).…”