Publication:
miRNAs as radio-response biomarkers for breast cancer stem cells

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Date

2020-02-06

Authors

Griñán-Lisón, Carmen
Olivares-Urbano, María Auxiliadora
Jiménez, Gema
López-Ruiz, Elena
Del Val, Coral
Morata-Tarifa, Cynthia
Entrena, José Manuel
González-Ramírez, Amanda Rocío
Boulaiz, Houria
Zurita Herrera, Mercedes

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FEBS Press and John Wiley & Sons
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Abstract

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.

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Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on Aldehyde or Oxo Group Donors::Aldehyde Oxidoreductases::Aldehyde Dehydrogenase
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms
Medical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Organisms::Eukaryota::Animals::Animal Population Groups::Animals, Laboratory::Animals, Inbred Strains::Mice, Inbred Strains::Mice, Inbred NOD
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, SCID
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs
Medical Subject Headings::Anatomy::Cells::Stem Cells::Neoplastic Stem Cells::Embryonal Carcinoma Stem Cells
Medical Subject Headings::Phenomena and Processes::Physical Phenomena::Radiation::Radiation, Ionizing
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Tyrosine Kinases::Receptor Protein-Tyrosine Kinases::Receptor, erbB-2
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Progesterone
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Statistics, Nonparametric
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Drug Evaluation, Preclinical::Drug Screening Assays, Antitumor::Xenograft Model Antitumor Assays

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Keywords

Biomarkers, Breast cancer, CSCs, miRNAs, Radiation, Radiotherapy, Biomarcadores, Neoplasias de la mama, MicroARNs, Radiación, Radioterapia

Citation

Griñán-Lisón C, Olivares-Urbano MA, Jiménez G, López-Ruiz E, Del Val C, Morata-Tarifa C, et al. miRNAs as radio-response biomarkers for breast cancer stem cells. Mol Oncol. 2020 Mar;14(3):556-570