Journal article

Small extracellular vesicle-derived miR-574-5p regulates PGE2-biosynthesis via TLR7/8 in lung cancer


Authors listDonzelli, Julia; Proestler, Eva; Riedel, Anna; Nevermann, Sheila; Hertel, Brigitte; Guenther, Andreas; Gattenloehner, Stefan; Savai, Rajkumar; Larsson, Karin; Saul, Meike J.

Publication year2021

JournalJournal of Extracellular Vesicles

Volume number10

Issue number12

eISSN2001-3078

Open access statusGold

PublisherWiley


Abstract
Intercellular communication plays an essential role in lung cancer (LC). One of the major players in cell-cell-communication is small extracellular vesicles (sEV). SEV trigger various biological responses by transporting cellular cargo to target cells. One essential sEV component are microRNAs (miRs), whose transport has recently attracted increasing research interest. We report that prostaglandin E-2 (PGE(2)), a key inflammatory lipid mediator, specifically induces the sorting of miR-574-5p in sEV of A549 and 2106T cells. We found that sEV-derived miR-574-5p activates Toll-like receptors (TLR) 7/8, thereby decreasing PGE(2)-levels. In contrast, intracellular miR-574-5p induces PGE(2)-biosynthesis. Consequently, the combination of intracellular and sEV-derived miR-574-5p controls PGE(2)-levels via a feedback loop. This was only observed in adeno- but not in squamous cell carcinoma, indicating a cell-specific response to sEV-derived miRs, which might be due to unique tetraspanin compositions. Hence, we describe a novel function of miR-574-5p unique to adenocarcinoma. Intracellular miR-574-5p induces PGE(2) and thus the secretion of sEV-derived miR-574-5p, which in turn decreases PGE(2)-biosynthesis in recipient cells.



Citation Styles

Harvard Citation styleDonzelli, J., Proestler, E., Riedel, A., Nevermann, S., Hertel, B., Guenther, A., et al. (2021) Small extracellular vesicle-derived miR-574-5p regulates PGE2-biosynthesis via TLR7/8 in lung cancer, Journal of Extracellular Vesicles, 10(12), Article 12143

APA Citation styleDonzelli, J., Proestler, E., Riedel, A., Nevermann, S., Hertel, B., Guenther, A., Gattenloehner, S., Savai, R., Larsson, K., & Saul, M. (2021). Small extracellular vesicle-derived miR-574-5p regulates PGE2-biosynthesis via TLR7/8 in lung cancer. Journal of Extracellular Vesicles. 10(12), Article 12143.



Keywords


extracellular vesicles (sEV)MICRORNASmicrosomal prostaglandin E synthase 1 (mPGES-1)miR-574-5pprostaglandin E2 (PGE2)PROSTAGLANDIN-E SYNTHASEtoll-like receptor 7/8 (TLR7/8)

Last updated on 2025-10-06 at 11:31