title: MicroRNA Profile in Response to Doxorubicin Treatment in Breast Cancer.
abstract: Chemotherapy treatment is the standard in triple negative breast cancers, a cancer subgroup which lacks a specific target. The mechanisms leading to the response, as well as any markers that allow the differentiation between responder and non-responder groups prior to treatment are unknown. In parallel, miRNAs can act as oncogenes or tumor suppressors and there is evidence of their involvement in promoting resistance to anticancer drugs. Therefore we hypothesized that changes in miRNA expression after doxorubicin treatment may also be relevant in treatment response.
  
  
  OBJECTIVE
  To study miRNAs that are differentially expressed in response to doxorubicin treatment.
  
  
  METHODS
  One luminal-A and two triple negative, breast cancer cell lines were exposed to doxorubicin. Microarray analysis was performed to identify the common and differentially modified miRNAs. Genes and pathways that are theoretically regulated by these miRNAs were analyzed.
  
  
  RESULTS
  Thirteen miRNAs common to all three lines were modified, in addition to 25 that were specific to triple negative cell lines, and 69 that changed only in the luminal-A cell line. This altered expression pattern seemed to be more strongly related to the breast cancer subgroup than to the treatment. The analysis of target genes revealed that cancer related pathways were the most affected by these miRNAs, moreover many of them had been previously related to chemotherapy resistance; thus suggesting follow-up studies. Additionally, through functional assays, we showed that miR-548c-3p is implicated in doxorubicin-treated MCF-7 cell viability, suggesting a role for this miRNA in resistance.
authors: INCLIVA Biomedical Research Institute, Valencia, Spain.
authors: Eduardo
authors: E
authors: Tormo
authors: INCLIVA Biomedical Research Institute, Valencia, Spain.
authors: Begoña
authors: B
authors: Pineda
authors: Unidad Central de, Investigación en Medicina-INCLIVA, Universitat de Valencia, Valencia, Spain.
authors: Eva
authors: E
authors: Serna
authors: INCLIVA Biomedical Research Institute, Valencia, Spain.
authors: Alba
authors: A
authors: Guijarro
authors: INCLIVA Biomedical Research Institute, Valencia, Spain.
authors: Gloria
authors: G
authors: Ribas
authors: INCLIVA Biomedical Research Institute, Valencia, Spain.
authors: Jaume
authors: J
authors: Fores
authors: INCLIVA Biomedical Research Institute, Valencia, Spain.
authors: Enrique
authors: E
authors: Chirivella
authors: INCLIVA Biomedical Research Institute, Valencia, Spain.
authors: Joan
authors: J
authors: Climent
authors: INCLIVA Biomedical Research Institute, Valencia, Spain.|Department of Hematology and Medical Oncology, Hospital Clínico Universitario de, Valencia, Spain.
authors: Ana
authors: A
authors: Lluch
authors: INCLIVA Biomedical Research Institute, Valencia, Spain.
authors: Pilar
authors: P
authors: Eroles
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods
chemical_list: D000903:Antibiotics, Antineoplastic; C561887:MIRN548 microRNA, human; D035683:MicroRNAs; D004317:Doxorubicin
keywords: BREAST CANCER; DOXORUBICIN; MIRNA