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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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.

Detaljer

Författare
  • Rosaria Benedetti
  • Chiara Papulino
  • Giulia Sgueglia
  • Ugo Chianese
  • Tommaso De Marchi
  • Francesco Iovino
  • Dante Rotili
  • Antonello Mai
  • Emma Niméus
  • Carmela Dell’ Aversana
  • Lucia Altucci
Enheter & grupper
Externa organisationer
  • Sapienza University of Rome
  • Skåne University Hospital
  • University of Campania Luigi Vanvitelli
  • Institute Experimental Endocrinology and Oncology "Gaetano Salvatore" (IEOS
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Cancer och onkologi

Nyckelord

Originalspråkengelska
Artikelnummer543
Antal sidor19
TidskriftCancers
Volym13
Utgåva nummer3
StatusPublished - 2021
PublikationskategoriForskning
Peer review utfördJa