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Radiotherapy-induced overexpression of exosomal miRNA-378a-3p in cancer cells limits natural killer cells cytotoxicity

Abstract : Aim: We here hypothesized that tumor-derived exosomal miRNA (TexomiR) released from irradiated tumors may play a role in the tumor cells escape to natural killer (NK) cells. Materials & methods: Our study included the use of different cancer cell lines, blood biopsies of xenograph mice model and patients treated with radiotherapy. Results: The irradiation of cancer cells promotes the TET2-mediated demethylation of miR-378 promoter, miR-378a-3p overexpression and its loading in exosomes, inducing the decrease of granzyme-B (GZMB) secretion by NK cells. An inverse correlation between TexomiR-378a-3p and GZMB was observed in murine and human blood samples. Conclusion: Our work identifies TexomiR-378a-3p as a molecular signature associated with the loss of NK cells cytotoxicity via the decrease of GZMB expression upon radiotherapy.
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https://www.hal.inserm.fr/inserm-03498832
Contributor : Elizabeth Bernardo Connect in order to contact the contributor
Submitted on : Tuesday, December 21, 2021 - 11:07:19 AM
Last modification on : Wednesday, September 7, 2022 - 11:32:04 AM

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Joséphine Briand, Delphine Garnier, Arulraj Nadaradjane, Karen Clément-Colmou, Vincent Potiron, et al.. Radiotherapy-induced overexpression of exosomal miRNA-378a-3p in cancer cells limits natural killer cells cytotoxicity. Epigenomics, Future Medicine, 2020, 12 (5), pp.397-408. ⟨10.2217/epi-2019-0193⟩. ⟨inserm-03498832⟩

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