Hsa-miR-155-5p drives aneuploidy at early stages of cellular transformation

• Published in: Oncotarget 2018-02, Vol.9 (16), p.13036-13047
• Main Authors: Pagotto, Sara, Veronese, Angelo, Soranno, Alessandra, Lanuti, Paola, Di Marco, Mirco, Russo, Marco Vincenzo, Ramassone, Alice, Marchisio, Marco, Simeone, Pasquale, Guanciali-Franchi, Paolo E, Palka, Giandomenico, Costantini, Renato Mariani, Croce, Carlo M, Visone, Rosa
• Format: Article
• Language: English
• Subjects: Research Paper
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.24437

is overexpressed in most solid and hematological malignancies. It promotes loss of genomic integrity in cancer cells by targeting genes involved in microsatellite instability and DNA repair; however, the link between and aneuploidy has been scarcely investigated. Here we describe a novel mechanism by which causes chromosomal instability. Using osteosarcoma cells (U2OS) and normal human dermal fibroblast (HDF), two well-established models for the study of chromosome congression, we demonstrate that targets the spindle checkpoint proteins BUB1, CENP-F, and ZW10, thus compromising chromosome alignment at the metaphase plate. In U2OS cells, exogenous expression reduced the recruitment of BUB1, CENP-F, and ZW10 to the kinetochores which resulted in defective chromosome congression. In contrast, during transformation of HDF by enforced expression of SV40 Large T antigen and human telomerase (HDF ), inhibition of reduced chromosome congression errors and aneuploidy at early passages. Using live-cell imaging we observed that delays progression through mitosis, indicating an activated mitotic spindle checkpoint, which likely fails to reduce aneuploidy. Overall, this study provides insight into a mechanism that generates aneuploidy at early stages of cellular transformation, pointing to a role for in chromosomal instability at tumor onset.