miRNAs as radio-response biomarkers for breast cancer stem cells

Mol Oncol. 2020 Mar;14(3):556-570. doi: 10.1002/1878-0261.12635. Epub 2020 Feb 6.


In breast cancer (BC), the presence of cancer stem cells (CSCs) has been related to relapse, metastasis, and radioresistance. Radiotherapy (RT) is an extended BC treatment, but is not always effective. CSCs have several mechanisms of radioresistance in place, and some miRNAs are involved in the cellular response to ionizing radiation (IR). Here, we studied how IR affects the expression of miRNAs related to stemness in different molecular BC subtypes. Exposition of BC cells to radiation doses of 2, 4, or 6 Gy affected their phenotype, functional characteristics, pluripotency gene expression, and in vivo tumorigenic capacity. This held true for various molecular subtypes of BC cells (classified by ER, PR and HER-2 status), and for BC cells either plated in monolayer, or being in suspension as mammospheres. However, the effect of IR on the expression of eight stemness- and radioresistance-related miRNAs (miR-210, miR-10b, miR-182, miR-142, miR-221, miR-21, miR-93, miR-15b) varied, depending on cell line subpopulation and clinicopathological features of BC patients. Therefore, clinicopathological features and, potentially also, chemotherapy regimen should be both taken into consideration, for determining a potential miRNA signature by liquid biopsy in BC patients treated with RT. Personalized and precision RT dosage regimes could improve the prognosis, treatment, and survival of BC patients.

Keywords: CSCs; biomarkers; breast cancer; miRNAs; radiation; radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Dehydrogenase 1 Family / metabolism
  • Animals
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / radiotherapy*
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Humans
  • Mice, Inbred NOD
  • Mice, SCID
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / radiation effects
  • Precision Medicine
  • Radiation, Ionizing
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Statistics, Nonparametric
  • Xenograft Model Antitumor Assays


  • Biomarkers, Tumor
  • MicroRNAs
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Aldehyde Dehydrogenase 1 Family
  • ERBB2 protein, human
  • Receptor, ErbB-2