Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells.

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dc.contributor.authorLobos-González, Lorena
dc.contributor.authorBustos, Rocío
dc.contributor.authorCampos, América
dc.contributor.authorSilva, Valeria
dc.contributor.authorSilva, Verónica
dc.contributor.authorJeldes, Emanuel
dc.contributor.authorSalomon, Carlos
dc.contributor.authorVaras-Godoy, Manuel
dc.contributor.authorCáceres-Verschae, Albano
dc.contributor.authorDurán, Eduardo
dc.contributor.authorVera, Tamara
dc.contributor.authorEzquer, Fernando
dc.contributor.authorEzquer, Marcelo
dc.contributor.authorBurzio, Verónica
dc.contributor.authorVillegas, Jaime
dc.date.accessioned2020-03-27T16:08:05Z
dc.date.available2020-03-27T16:08:05Z
dc.date.issued2020
dc.descriptionCentro de Medicina Regenerativa
dc.description.abstractDuring intercellular communication, cells release extracellular vesicles such as exosomes, which contain proteins, ncRNAs and mRNAs that can influence proliferation and/or trigger apoptosis in recipient cells, and have been proposed to play an essential role in promoting invasion of tumor cells and in the preparation of metastatic niches. Our group proposed the antisense non-coding mitochondrial RNA (ASncmtRNA) as a new target for cancer therapy. ASncmtRNA knockdown using an antisense oligonucleotide (ASO-1537S) causes massive death of tumor cells but not normal cells and strongly reduces metastasis in mice. In this work, we report that exosomes derived from ASO-1537S-treated MDA-MB-231 breast cancer cells (Exo-1537S) inhibits tumorigenesis of recipient cells, in contrast to exosomes derived from control-ASO-treated cells (Exo-C) which, in contrast, enhance these properties. Furthermore, an in vivo murine peritoneal carcinomatosis model showed that Exo-1537S injection reduced tumorigenicity compared to controls. Proteomic analysis revealed the presence of Lactadherin and VE-Cadherin in exosomes derived from untreated cells (Exo-WT) and Exo-C but not in Exo-1537S, and the latter displayed enrichment of proteasomal subunits. These results suggest a role for these proteins in modulation of tumorigenic properties of exosome-recipient cells. Our results shed light on the mechanisms through which ASncmtRNA knockdown affects the preparation of breast cancer metastatic niches in a peritoneal carcinomatosis model.
dc.identifier.citationSci Rep. 2020 Jan 15;10(1):343. doi: 10.1038/s41598-019-57018-1.
dc.identifier.urihttp://hdl.handle.net/11447/3187
dc.identifier.urihttps://doi.org/10.1038/s41598-019-57018-1
dc.language.isoen
dc.publisherNature Publishing Group
dc.subjectBreast cancer
dc.subjectMitochondrial ASncmtRNA
dc.titleExosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells.
dc.typeArticle

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