Epigenetic silencing of miR-145-5p contributes to brain metastasis

Sara Donzelli, Federica Mori, Teresa Bellissimo, Andrea Sacconi, Beatrice Casini, Tania Frixa, Giuseppe Roscilli, Luigi Aurisicchio, Francesco Facciolo, Alfredo Pompili, Maria Antonia Carosi, Edoardo Pescarmona, Oreste Segatto, Greg Pond, Paola Muti, Stefano Telera, Sabrina Strano, Yosef Yarden, Giovanni Blandino

Research output: Contribution to journalArticle

Abstract

Brain metastasis is a major cause of morbidity and mortality of lung cancer patients. We assessed whether aberrant expression of specific microRNAs could contribute to brain metastasis. Comparison of primary lung tumors and their matched metastatic brain disseminations identified shared patterns of several microRNAs, including common down-regulation of miR-145-5p. Down-regulation was attributed to methylation of miR-145's promoter and affiliated elevation of several protein targets, such as EGFR, OCT-4, MUC-1, c-MYC and, interestingly, tumor protein D52 (TPD52). In line with these observations, restored expression of miR-145-5p and selective depletion of individual targets markedly reduced in vitro and in vivo cancer cell migration. In aggregate, our results attribute to miR-145-5p and its direct targets pivotal roles in malignancy progression and in metastasis.

Original languageEnglish
Pages (from-to)35183-35201
Number of pages19
JournalOncotarget
Volume6
Issue number34
DOIs
Publication statusPublished - 2015

Keywords

  • Brain metastases
  • Epigenetic modifications
  • Lung cancer
  • Migration
  • Mir-145-5p

ASJC Scopus subject areas

  • Oncology

Fingerprint Dive into the research topics of 'Epigenetic silencing of miR-145-5p contributes to brain metastasis'. Together they form a unique fingerprint.

  • Cite this

    Donzelli, S., Mori, F., Bellissimo, T., Sacconi, A., Casini, B., Frixa, T., Roscilli, G., Aurisicchio, L., Facciolo, F., Pompili, A., Carosi, M. A., Pescarmona, E., Segatto, O., Pond, G., Muti, P., Telera, S., Strano, S., Yarden, Y., & Blandino, G. (2015). Epigenetic silencing of miR-145-5p contributes to brain metastasis. Oncotarget, 6(34), 35183-35201. https://doi.org/10.18632/oncotarget.5930