Mir-214 and mir-148b targeting inhibits dissemination of melanoma and breast cancer

Francesca Orso, Lorena Quirico, Federico Virga, Elisa Penna, Daniela Dettori, Daniela Cimino, Roberto Coppo, Elena Grassi, Angela Rita Elia, Davide Brusa, Silvia Deaglio, Maria Felice Brizzi, Michael B. Stadler, Paolo Provero, Michele Caselle, Daniela Taverna

Research output: Contribution to journalArticle

Abstract

miR-214 and miR-148b have been proposed to antagonize the effects of each other in enabling or blocking metastasis, respectively. In this study, we provide evidence deepening their role and interrelationship in the process of metastatic dissemination. Depleting miR-214 or elevating miR-148b blocked the dissemination of melanoma or breast cancer cells, an effect that could be accentuated by dual alteration. Mechanistic investigations indicated that dual alteration suppressed passage of malignant cells through the blood vessel endothelium by reducing expression of the cell adhesion molecules ITGA5 and ALCAM. Notably, transendothelial migration in vitro and extravasation in vivo impaired by singly alternating miR-214 or miR-148b could be overridden by overexpression of ITGA5 or ALCAM in the same tumor cells. In clinical specimens of primary breast cancer or metastatic melanoma, we found a positive correlation between miR-214 and ITGA5 or ALCAM along with an inverse correlation of miR-214 and miR-148b in the same specimens. Our findings define an antagonistic relationship of miR-214 and miR-148b in determining the dissemination of cancer cells via tumor-endothelial cell interactions, with possible implications for microRNA-mediated therapeutic interventions aimed at blocking cancer extravasation.
Original languageEnglish
Pages (from-to)5151 - 5162
Number of pages12
JournalCancer Research
Volume76
Issue number17
DOIs
Publication statusPublished - Sep 1 2016

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ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Orso, F., Quirico, L., Virga, F., Penna, E., Dettori, D., Cimino, D., Coppo, R., Grassi, E., Elia, A. R., Brusa, D., Deaglio, S., Brizzi, M. F., Stadler, M. B., Provero, P., Caselle, M., & Taverna, D. (2016). Mir-214 and mir-148b targeting inhibits dissemination of melanoma and breast cancer. Cancer Research, 76(17), 5151 - 5162. https://doi.org/10.1158/0008-5472.CAN-15-1322