MiR-216a acts as a negative regulator of breast cancer by modulating stemness properties and tumor microenvironment

Giuseppina Roscigno, Assunta Cirella, Alessandra Affinito, Cristina Quintavalle, Iolanda Scognamiglio, Francesco Palma, Francesco Ingenito, Silvia Nuzzo, Francesca De Micco, Antonio Cuccuru, Renato Thomas, Gerolama Condorelli

Research output: Contribution to journalArticlepeer-review

Abstract

Breast cancer is the most frequent malignancy in females in terms of both incidence and mortality. Underlying the high mortality rate is the presence of cancer stem cells, which divide indefinitely and are resistant to conventional chemotherapies, so causing tumor relapse. In the present study, we identify miR-216a-5p as a downregulated microRNA in breast cancer stem cells vs. the differentiated counterpart. We demonstrate that overexpression of miR-216a-5p impairs stemness markers, mammosphere formation, ALDH activity, and the level of Toll-like receptor 4 (TLR4), which plays a significant role in breast cancer progression and metastasis by leading to the release of pro-inflammatory molecules, such as interleukin 6 (IL-6). Indeed, miR-216a regulates the crosstalk between cancer cells and the cells of the microenvironment, in particular cancer-associated fibroblasts (CAFs), through regulation of the TLR4/IL6 pathway. Thus, miR-216a has an important role in the regulation of stem phenotype, decreasing stem-like properties and affecting the cross-talk between cancer cells and the tumor microenvironment.

Original languageEnglish
Article number2313
JournalInternational Journal of Molecular Sciences
Volume21
Issue number7
DOIs
Publication statusPublished - Apr 1 2020

Keywords

  • Breast cancer
  • Cancer stem cells
  • MicroRNA
  • Tumor microenvironment

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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