MiR-135b coordinates progression of ErbB2-driven mammary carcinomas through suppression of MID1 and MTCH2

Maddalena Arigoni, Giuseppina Barutello, Federica Riccardo, Elisabetta Ercole, Daniela Cantarella, Francesca Orso, Laura Conti, Stefania Lanzardo, Daniela Taverna, Irene Merighi, Raffaele A. Calogero, Federica Cavallo, Elena Quaglino

Research output: Contribution to journalArticlepeer-review

Abstract

In an attempt to reveal deregulated miRNAs associated with the progression of carcinomas developed in BALB-neuT transgenic mice, we found increased expression of miR-135b during malignancy. Relevantly, we observed that miR-135b is up-regulated in basal or normal-like human breast cancers, and it correlates with patient survival and early metastatization. Therefore, we investigated its biological functions by modulating its expression (up- or down-regulation) in mammary tumor cells. Although no effect was observed on proliferation in cell culture and in orthotopically injected mice, miR-135b was able to control cancer cell stemness in a mammosphere assay, anchorage-independent growth in vitro, and lung cancer cell dissemination in mice after tail vein injections. Focusing on the miR-135b molecular mechanism, we observed that miR-135b controls malignancy via its direct targets, midline 1 (MID1) and mitochondrial carrier homolog 2 (MTCH2), as proved by biochemical and functional rescuing/phenocopying experiments. Consistently, an anti-correlation between miR-135b and MID1 or MTCH2 was found in human primary tumor samples. In conclusion, our research led us to the identification of miR-135b and its targets, MID1 and MTCH2, as relevant coordinators of mammary gland tumor progression.

Original languageEnglish
Pages (from-to)2058-2070
Number of pages13
JournalAmerican Journal of Pathology
Volume182
Issue number6
DOIs
Publication statusPublished - Jun 2013

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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