Naslov
MiR-214 in tumor-stroma cell interactions

Autori
Orso, Francesca ; Virga, Federico ; Dettori, Daniela ; Paradzik, Mladen ; Baruffaldi, Desiree ; Massa, Annamaria ; Van Wynendaele, Marie ; Bolli, Elisabetta ; Cavallo, Federica ; Forni, Marco ; Salmena, Leonardo ; Mazzone, Massimiliano ; Pandolfi, Pier Paolo ; Taverna, Daniela

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract book / - , 2019, 33-33

Skup
61st annual meeting of the Italian cancer society

Mjesto i datum
Napulj, Italija, 06.11.2019. - 08.11.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
miR-214, stroma cells, tumor

Sažetak
MicroRNAs (miRs) are small non-coding RNAs that act as negative regulators of gene expression and control tumor progression. We previously demonstrated that miR-214 is upregulated in malignant melanomas and triple negative breast tumors and promotes metastatic dissemination by affecting a complex pathway including transcription factors and adhesion molecules as well as the anti-metastatic miR-148b. Importantly, tumor dissemination can be reduced by blocking miR-214 function or increasing miR-148b expression and further impaired by simultaneous interventions, thus suggesting that the miR-214/miR-148b axis can be exploited for miR-based therapeutic approaches. Interestingly, we evidenced that miR-214 is highly expressed in various stroma cells and it correlates with a stroma signature in human tumors. Moreover, we found miR-214 in stroma cells and observed that miR-214 expression in tumor cells is strongly influenced by stroma cells. In order to explore the function of miR-214 in the crosstalk between tumor and stroma cells, we evaluated tumor formation and progression in immunocompetent mice carrying a total-body miR-214 deletion (miR-214KO mice) or overexpression (miR-214OVER mice) crossed with MMTV-PyMT mice or used as recipients for tumor transplants. While growth of endogenous or transplanted tumors was similar for all animals, metastasis formation in distant organs was diminished in miR-214KO mice while increased in miR-214OVER mice. We are now investigating the mechanism leading to altered aggressiveness. We have evidence of increased epithelial-mesenchymal transition and established inflammation in the primary tumor and increased macrophage recruitment in distant organs (before metastasis formation) when enhanced dissemination is observed, therefore suggesting the relevance of stromal miR-214 in tumor progression. In parallel, we are trying to set the bases for possible therapeutic interventions based on miR-214 in tumor stroma cells.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA