The efficacy and side effects of endocrine therapy in breast cancer (BC) depend largely on estrogen receptor alpha (ERα) expression, the specific drug administered, and treatment scheduling. Although the benefits of endocrine therapy outweigh any adverse effects in the initial stages of BC, later- or advanced-stage tumors acquire resistance to treatments. The mechanisms underlying tumor resistance to therapy are still not well understood, posing a major challenge for BC patient care. Epigenetic regulation and miRNA expression may be involved in the switch from a treatment-sensitive to a treatment-resistant state and could provide a valid therapeutic strategy for ERα negative BC. Here, a hybrid lysine-specific histone demethylase inhibitor, MC3324, displaying selective estrogen receptor down-regulator-like activities in BC, was used to highlight the interplay between epigenetic and ERα signaling. MC3324 anticancer action is mediated by microRNA (miRNA) expression regulation, indicating an innovative function for this molecule. Integrated analysis suggests a crosstalk between estrogen signaling, ERα interactors, miRNAs, and their putative targets. Specifically, miR-181a-5p expression is regulated by MC3324 and has an impact on cellular levels of ERα. A comparison of breast tumor versus healthy mammary tissues confirmed the important role of miR-181a-5p in ERα regulation and points to its putative predictive function in BC therapy.

Regulatory interplay between mir-181a-5p and estrogen receptor signaling cascade in breast cancer / Benedetti, R.; Papulino, C.; Sgueglia, G.; Chianese, U.; De Marchi, T.; Iovino, F.; Rotili, D.; Mai, A.; Nimeus, E.; Aversana, C. D.; Altucci, L.. - In: CANCERS. - ISSN 2072-6694. - 13:3(2021), pp. 1-19. [10.3390/cancers13030543]

Regulatory interplay between mir-181a-5p and estrogen receptor signaling cascade in breast cancer

Rotili D.;Mai A.;
2021

Abstract

The efficacy and side effects of endocrine therapy in breast cancer (BC) depend largely on estrogen receptor alpha (ERα) expression, the specific drug administered, and treatment scheduling. Although the benefits of endocrine therapy outweigh any adverse effects in the initial stages of BC, later- or advanced-stage tumors acquire resistance to treatments. The mechanisms underlying tumor resistance to therapy are still not well understood, posing a major challenge for BC patient care. Epigenetic regulation and miRNA expression may be involved in the switch from a treatment-sensitive to a treatment-resistant state and could provide a valid therapeutic strategy for ERα negative BC. Here, a hybrid lysine-specific histone demethylase inhibitor, MC3324, displaying selective estrogen receptor down-regulator-like activities in BC, was used to highlight the interplay between epigenetic and ERα signaling. MC3324 anticancer action is mediated by microRNA (miRNA) expression regulation, indicating an innovative function for this molecule. Integrated analysis suggests a crosstalk between estrogen signaling, ERα interactors, miRNAs, and their putative targets. Specifically, miR-181a-5p expression is regulated by MC3324 and has an impact on cellular levels of ERα. A comparison of breast tumor versus healthy mammary tissues confirmed the important role of miR-181a-5p in ERα regulation and points to its putative predictive function in BC therapy.
breast cancer; endocrine therapy; epigenetic SERD; ERα; hormone signaling; MiR-181a-5p
01 Pubblicazione su rivista::01a Articolo in rivista
Regulatory interplay between mir-181a-5p and estrogen receptor signaling cascade in breast cancer / Benedetti, R.; Papulino, C.; Sgueglia, G.; Chianese, U.; De Marchi, T.; Iovino, F.; Rotili, D.; Mai, A.; Nimeus, E.; Aversana, C. D.; Altucci, L.. - In: CANCERS. - ISSN 2072-6694. - 13:3(2021), pp. 1-19. [10.3390/cancers13030543]
File allegati a questo prodotto
File Dimensione Formato  
Benedetti_Regulatory-interplay_2021.pdf

accesso aperto

Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 5.35 MB
Formato Adobe PDF
5.35 MB Adobe PDF Visualizza/Apri PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1503800
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 6
social impact