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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/175775
Hsa-miR155-5p up-regulation in Breast Cancer and its relevance for treatment with Poly [ADP-ribose] polymerase 1 (PARP-1) inhibitors
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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.
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PASCULLI, Barbara, et al. Hsa-miR155-5p up-regulation in Breast Cancer and its relevance for treatment with Poly [ADP-ribose] polymerase 1 (PARP-1) inhibitors. Frontiers In Oncology. 2020. Vol. 10. ISSN 2234-943X. [consulted: 14 of June of 2026]. Available at: https://hdl.handle.net/2445/175775