miRNAs as radio-response biomarkers for breast cancer stem cells
MetadataShow full item record
AuthorGriñán Lisón, Carmen; Olivares Urbano, María Auxiliadora; Jiménez, Gema; López Ruiz, Elena; Val Muñoz, María Coral Del; Morata-Tarifa, Cynthia; Entrena, José Manuel; González Ramírez, Amanda Rocío; Boulaiz Tassi, Houria; Zurita Herrera, Mercedes; Núñez Torres, María Isabel; Marchal Corrales, Juan Antonio
Griñán‐Lisón, C., Olivares‐Urbano, M. A., Jiménez, G., López‐Ruiz, E., del Val, C., Morata‐Tarifa, C., ... & Núñez, M. I. (2020). miRNAs as radio‐response biomarkers for breast cancer stem cells. Molecular Oncology.
SponsorshipThis work has been partially funded by the Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía and European Regional Development Fund (ERDF), ref. SOMM17/6109/ UGR, and with grants from the Ministry of Economy and Competitiveness (FEDER funds, projects no. PIE16/00045) and from the Chair ‘Doctors Galera- Requena in cancer stem cell research’ (CMC-CTS963).
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.