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MiRNAs as radio-response biomarkers for breast cancer stem cells.

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.

SUBMITTER: Grinan-Lison C

PROVIDER: S-EPMC7053246 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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miRNAs as radio-response biomarkers for breast cancer stem cells.

Griñán-Lisón Carmen C Olivares-Urbano María Auxiliadora MA Jiménez Gema G López-Ruiz Elena E Del Val Coral C Morata-Tarifa Cynthia C Entrena José Manuel JM González-Ramírez Amanda Rocío AR Boulaiz Houria H Zurita Herrera Mercedes M Núñez María Isabel MI Marchal Juan Antonio JA

Molecular oncology 20200206 3

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 ...[more]

PMID: 31930680

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Project description:ObjectivesThe impact of N7-methylguanosine (m7G) on tumor progression and the regulatory role of microRNAs (miRNAs) in immune function significantly influence breast cancer (BC) prognosis. Investigating the interplay between m7G modification and miRNAs provides novel insights for assessing prognostics and drug responses in BC.Materials and methodsRNA sequences (miRNA and mRNA profiles) and clinical data for BC were acquired from the Cancer Genome Atlas (TCGA) database. A miRNA signature associated with 15 m7G in this cohort was identified using Cox regression and LASSO. The risk score model was evaluated using Kaplan-Meier and time-dependent ROC analysis, categorizing patients into high-risk and low-risk groups. Functional enrichment analyses were conducted to explore potential pathways. The immune system, including scores, cell infiltration, function, and drug sensitivity, was examined and compared between high-risk and low-risk groups. A nomogram that combines risk scores and clinical factors was developed and validated. Single-sample gene set enrichment analysis (ssGSEA) was employed to explore m7G-related miRNA signatures and immune cell relationships in the tumor microenvironment. Additionally, drug susceptibility was compared between risk groups.ResultsFifteen m7G-related miRNAs were independently correlated with overall survival (OS) in BC patients. Time-dependent ROC analysis yielded area under the curve (AUC) values of 0.742, 0.726, and 0.712 for predicting 3-, 5-, and 10-year survival rates, respectively. The Kaplan-Meier analysis revealed a significant disparity in OS between the high-risk and low-risk groups (p = 1.3e-6). Multiple regression identified the risk score as a significant independent prognostic factor. An excellent calibration nomogram with a C-index of 0.785 (95 % CI: 0.728-0.843) was constructed. In immune analysis, low-risk patients exhibited heightened immune function and increased responsiveness to immunotherapy and chemotherapy compared to high-risk patients.ConclusionThis study systematically analyzed m7G-related miRNAs and revealed their regulatory mechanisms concerning the tumor microenvironment (TME), pathology, and the prognosis of BC patient. Based on these miRNAs, a prognostic model and nomogram were developed for BC patients, facilitating prognostic assessments. These findings can also assist in predicting treatment responses and guiding medication selection.

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MiRNAs as radio-response biomarkers for breast cancer stem cells.

Publications

miRNAs as radio-response biomarkers for breast cancer stem cells.

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