New insights into radioresistance in breast cancer identify a dual function of miR‐122 as a tumor suppressor and oncomiR

• Published in: Molecular oncology Vol. 13; no. 5; pp. 1249 - 1267
• Main Authors: Perez‐Añorve, Isidro X., Gonzalez‐De la Rosa, Claudia H., Soto‐Reyes, Ernesto, Beltran‐Anaya, Fredy O., Del Moral‐Hernandez, Oscar, Salgado‐Albarran, Marisol, Angeles‐Zaragoza, Oscar, Gonzalez‐Barrios, Juan A., Landero‐Huerta, Daniel A., Chavez‐Saldaña, Margarita, Garcia‐Carranca, Alejandro, Villegas‐Sepulveda, Nicolas, Arechaga‐Ocampo, Elena
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.05.2019; John Wiley and Sons Inc; Wiley
• Subjects: Analysis; Arrays; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Neoplasms - radiotherapy; Cancer; Cancer therapies; Cell growth; Cell survival; Data analysis; Diseases; Experiments; Female; Gene expression; Gene Expression Regulation, Neoplastic - radiation effects; Genes, Tumor Suppressor; Genomes; Humans; Laboratories; MCF-7 Cells; MicroRNA; MicroRNAs; MicroRNAs - biosynthesis; MicroRNAs - genetics; miRNA; miR‐122; Neoplasm Proteins; Oncology, Experimental; Ontology; Phenotypes; Polymerase chain reaction; Radiation therapy; Radiation Tolerance; Radioresistance; Radiosensitivity; Relapse; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; Tumor cells; Tumor suppressor genes; Tumors; Up-Regulation - radiation effects; Massachusetts; United States > US; microRNAs; breast cancer; miR-122; radioresistance
• ISSN: 1574-7891; 1878-0261; 1878-0261
• DOI: 10.1002/1878-0261.12483

Radioresistance of tumor cells gives rise to local recurrence and disease progression in many patients. MicroRNAs (miRNAs) are master regulators of gene expression that control oncogenic pathways to modulate the radiotherapy response of cells. In the present study, differential expression profiling assays identified 16 deregulated miRNAs in acquired radioresistant breast cancer cells, of which miR‐122 was observed to be up‐regulated. Functional analysis revealed that miR‐122 has a role as a tumor suppressor in parental cells by decreasing survival and promoting radiosensitivity. However, in radioresistant cells, miR‐122 functions as an oncomiR by promoting survival. The transcriptomic landscape resulting from knockdown of miR‐122 in radioresistant cells showed modulation of the ZNF611, ZNF304, RIPK1, HRAS, DUSP8 and TNFRSF21 genes. Moreover, miR‐122 and the set of affected genes were prognostic factors in breast cancer patients treated with radiotherapy. Our data indicate that up‐regulation of miR‐122 promotes cell survival in acquired radioresistant breast cancer and also suggest that miR‐122 differentially controls the response to radiotherapy by a dual function as a tumor suppressor an and oncomiR dependent on cell phenotype. Radiotherapy exerts cytotoxic effects on primary tumor cells; nevertheless, some tumor cells eventually develop radioresistance via molecular reprogramming to acquire the ability to survive. miR‐122 has been categorized as a tumor suppressor in breast cancer. Here, we report a novel function of miR‐122 as an oncomiR in radioresistant breast cancer cells. OncomiR‐122 is essential to maintain the survival of radioresistant breast cancer cells via the control of a network of survival genes.