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2020-08-12

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cc-by (c) Pasculli, Bárbara et al., 2020
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: 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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https://doi.org/10.3389/fonc.2020.01415

Resum

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.

Matèries

Càncer de mama, Inhibidors enzimàtics, Oncogens

Matèries (anglès)

Breast cancer, Enzyme inhibitors, Oncogenes

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Articles publicats en revistes (Ciències Fisiològiques)

Citació

PASCULLI, Barbara, BARBANO, Raffaela, FONTANA, Andrea, BIAGINI, Tommaso, VIESTI, Maria pia di, RENDINA, Michelina, VALORI, Vanna maria, MORRITTI, Maria, BRAVACCINI, Sara, RAVAIOLI, Sara, MAIELLO, Evaristo, GRAZIANO, Paolo, MURGO, Roberto, COPETTI, Massimiliano, MAZZA, Tommaso, FAZIO, Vito michele, ESTELLER, Manel, PARRELLA, Paola. 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. [consulta: 25 de gener de 2026]. ISSN: 2234-943X. [Disponible a: https://hdl.handle.net/2445/175775]

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