Hsa-miR-155-5p Up-Regulation in Breast Cancer and Its Relevance for Treatment With Poly[ADP-Ribose] Polymerase 1 (PARP-1) Inhibitors

Barbara Pasculli, Raffaela Barbano, Andrea Fontana, Tommaso Biagini, Maria Pia Di Viesti, Michelina Rendina, Vanna Maria Valori, Maria Morritti, Sara Bravaccini, Sara Ravaioli, Evaristo Maiello, Paolo Graziano, Roberto Murgo, Massimiliano Copetti, Tommaso Mazza, Vito Michele Fazio, Manel Esteller, Paola Parrella

Research output: Contribution to journalArticlepeer-review

Abstract

miR-155-5p is a well-known oncogenic microRNA, showing frequent overexpression in human malignancies, including breast cancer. Here, we show that high miR-155-5p levels are associated with unfavorable prognostic factors in two independent breast cancer cohorts (CSS cohort, n = 283; and TCGA-BRCA dataset, n = 1,095). Consistently, miR-155-5p results as differentially expressed in the breast cancer subgroups identified by the surrogate molecular classification in the CSS cohort and the PAM50 classifier in TCGA-BRCA dataset, with the TNBC and HER2-amplified tumors carrying the highest levels. Since the analysis of TCGA-BC dataset also demonstrated a significant association between miR-155-5p levels and the presence of mutations in homologous recombination (HR) genes, we hypothesized that miR-155-5p might affect cell response to the PARP-1 inhibitor Olaparib. As expected, miR-155-5p ectopic overexpression followed by Olaparib administration resulted in a greater reduction of cell viability as compared to Olaparib administration alone, suggesting that miR-155-5p might induce a synthetic lethal effect in cancer cells when coupled with PARP-1-inhibition. Overall, our data point to a role of miR-155-5p in homologous recombination deficiency and suggest miR-155-5p might be useful in predicting response to PARP1 inhibitors in the clinical setting.

Original languageEnglish
Article number1415
JournalFrontiers in Oncology
Volume10
DOIs
Publication statusPublished - Aug 12 2020

Keywords

  • breast cancer
  • homologous recombination
  • hsa-miR-155-5p
  • Olaparib
  • PARP-1 inhibitors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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