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 wo...

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Main Authors: Yingxue Li, Shuling Cui, Zemin Xu, Yanping Zhang, Tao Wu, Jing Zhang, Yichen Chen
Format: Article
Language:English
Published: BMC 2022-06-01
Series:BMC Women's Health
Subjects:
Online Access:https://doi.org/10.1186/s12905-022-01827-6
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author Yingxue Li
Shuling Cui
Zemin Xu
Yanping Zhang
Tao Wu
Jing Zhang
Yichen Chen
author_facet Yingxue Li
Shuling Cui
Zemin Xu
Yanping Zhang
Tao Wu
Jing Zhang
Yichen Chen
author_sort Yingxue Li
collection DOAJ
description 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.
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spelling doaj.art-903c17726939490996fa8538a5bd2af72022-12-22T02:38:30ZengBMCBMC Women's Health1472-68742022-06-0122111110.1186/s12905-022-01827-6Exosomal tRF-Leu-AAG-001 derived from mast cell as a potential non-invasive diagnostic biomarker for endometriosisYingxue Li0Shuling Cui1Zemin Xu2Yanping Zhang3Tao Wu4Jing Zhang5Yichen Chen6Ningbo Institute of Medical SciencesThe Affiliated Hospital of Medical School of Ningbo UniversityAddiction Research of Zhejiang Province, Ningbo Kangning Hospital, School of Medicine, Ningbo UniversityNingbo UniversityThe Affiliated Hospital of Medical School of Ningbo UniversityNingbo Women&Children’s HospitalNingbo Women&Children’s HospitalAbstract 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.https://doi.org/10.1186/s12905-022-01827-6EndometriosisExosomesLeucorrheaTransfer RNA-derived fragmentDiagnostic biomarker
spellingShingle Yingxue Li
Shuling Cui
Zemin Xu
Yanping Zhang
Tao Wu
Jing Zhang
Yichen Chen
Exosomal tRF-Leu-AAG-001 derived from mast cell as a potential non-invasive diagnostic biomarker for endometriosis
BMC Women's Health
Endometriosis
Exosomes
Leucorrhea
Transfer RNA-derived fragment
Diagnostic biomarker
title Exosomal tRF-Leu-AAG-001 derived from mast cell as a potential non-invasive diagnostic biomarker for endometriosis
title_full Exosomal tRF-Leu-AAG-001 derived from mast cell as a potential non-invasive diagnostic biomarker for endometriosis
title_fullStr Exosomal tRF-Leu-AAG-001 derived from mast cell as a potential non-invasive diagnostic biomarker for endometriosis
title_full_unstemmed Exosomal tRF-Leu-AAG-001 derived from mast cell as a potential non-invasive diagnostic biomarker for endometriosis
title_short Exosomal tRF-Leu-AAG-001 derived from mast cell as a potential non-invasive diagnostic biomarker for endometriosis
title_sort exosomal trf leu aag 001 derived from mast cell as a potential non invasive diagnostic biomarker for endometriosis
topic Endometriosis
Exosomes
Leucorrhea
Transfer RNA-derived fragment
Diagnostic biomarker
url https://doi.org/10.1186/s12905-022-01827-6
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