tRNA-Derived Fragment tRF-17-79MP9PP Attenuates Cell Invasion and Migration via THBS1/TGF-β1/Smad3 Axis in Breast Cancer

Mo, Dongping; He, Fang; Zheng, Junyu; Chen, Huanhuan; Tang, Li; Yan, Feng

doi:10.3389/fonc.2021.656078

“…In other diseases, speci c tRF&tiRNA have also been gradually considered as reliable biomarkers (Chen et al, 2021). In breast cancer, Serum tRF-17-79MP9PP, as a biological marker for detecting breast cancer, has a sensitivity of up to 70% (Mo et al, 2021). These altogether supported the great potential of exosomal tRFs as biomarkers in the diagnosis of diseases.…”

Section: Discussionmentioning

confidence: 97%

Exosomal tRF-Leu-AAG-001 Derived from Mast Cell as a Potential Non-Invasive Diagnostic Biomarker for Endometriosis

Li

¹

,

Cui

²

,

Zhang

³

et al. 2021

Preprint

0

View full text Add to dashboard Cite

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.

show abstract

“…In other diseases, speci c tRF&tiRNA have also been gradually considered as reliable biomarkers [19] . In breast cancer, Serum tRF-17-79MP9PP, as a biological marker for detecting breast cancer, has a sensitivity of up to 70% [20] . These altogether supported the great potential of exosomal tRFs as biomarkers in the diagnosis of diseases.…”

Section: Discussionmentioning

confidence: 99%

Exosomal tRF-Leu-AAG-001 Derived from Mast Cell as a Potential Non-invasive Diagnostic Biomarker for Endometriosis

Li

¹

,

Cui

²

,

Xu

³

et al. 2022

Preprint

0

View full text Add to dashboard Cite

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.

show abstract

“…The tRF/miR-1280 derived from tRNA Leu and pre-miRNA inhibits Notch signaling pathway by directly targeting Notch ligand JAG2 mRNA 3′ UTR, inhibiting the growth and metastasis of colorectal cancer cells [ 18 ]. tRF-17-79MP9PP targets THBS1 3′ UTR to attenuate breast cancer cell invasion and migration [ 45 ]. In this study, we confirmed that NDFIP2 is the direct target of Gly-tRF.…”

Section: Discussionmentioning

confidence: 99%

Gly-tRF enhances LCSC-like properties and promotes HCC cells migration by targeting NDFIP2

Zhou

¹

,

Hu

²

,

Liu

³

et al. 2021

View full text Add to dashboard Cite

Background Accumulating evidence demonstrates that tRFs (tRNA-derived small RNA fragments) and tiRNAs (tRNA-derived stress-induced RNA), an emerging category of regulatory RNA molecules derived from transfer RNAs (tRNAs), are dysregulated in in various human cancer types and play crucial roles. However, their roles and mechanisms in hepatocellular carcinoma (HCC) and liver cancer stem cells (LCSCs) are still unknown. Methods The expression of glycine tRNA-derived fragment (Gly-tRF) was measured by qRT-PCR. Flow cytometric analysis and sphere formation assays were used to determine the properties of LCSCs. Transwell assays and scratch wound assays were performed to detect HCC cell migration. Western blotting was conducted to evaluate the abundance change of Epithelial-mesenchymal transition (EMT)-related proteins. Dual luciferase reporter assays and signalling pathway analysis were performed to explore the underlying mechanism of Gly-tRF functions. Results Gly-tRF was highly expressed in HCC cell lines and tumour tissues. Gly-tRF mimic increased the LCSC subpopulation proportion and LCSC-like cell properties. Gly-tRF mimic promoted HCC cell migration and EMT. Loss of Gly-tRF inhibited HCC cell migration and EMT. Mechanistically, Gly-tRF decreased the level of NDFIP2 mRNA by binding to the NDFIP2 mRNA 3′ UTR. Importantly, overexpression of NDFIP2 weakened the promotive effects of Gly-tRF on LCSC-like cell sphere formation and HCC cell migration. Signalling pathway analysis showed that Gly-tRF increased the abundance of phosphorylated AKT. Conclusions Gly-tRF enhances LCSC-like cell properties and promotes EMT by targeting NDFIP2 and activating the AKT signalling pathway. Gly-tRF plays tumor-promoting role in HCC and may lead to a potential therapeutic target for HCC.

show abstract

tRNA-Derived Fragment tRF-17-79MP9PP Attenuates Cell Invasion and Migration via THBS1/TGF-β1/Smad3 Axis in Breast Cancer

Cited by 47 publications

References 46 publications

Exosomal tRF-Leu-AAG-001 Derived from Mast Cell as a Potential Non-Invasive Diagnostic Biomarker for Endometriosis

Exosomal tRF-Leu-AAG-001 Derived from Mast Cell as a Potential Non-Invasive Diagnostic Biomarker for Endometriosis

Exosomal tRF-Leu-AAG-001 Derived from Mast Cell as a Potential Non-invasive Diagnostic Biomarker for Endometriosis

Gly-tRF enhances LCSC-like properties and promotes HCC cells migration by targeting NDFIP2

Contact Info

Product

Resources

About