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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Rosaria Benedetti
  • Chiara Papulino
  • Giulia Sgueglia
  • Ugo Chianese
  • Tommaso De Marchi
  • Francesco Iovino
  • Dante Rotili
  • Antonello Mai
  • Emma Niméus
  • Carmela Dell’ Aversana
  • Lucia Altucci
Organisations
External organisations
  • Sapienza University of Rome
  • Skåne University Hospital
  • University of Campania Luigi Vanvitelli
  • Institute Experimental Endocrinology and Oncology "Gaetano Salvatore" (IEOS
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • Breast cancer, Endocrine therapy, Epigenetic SERD, ERα, Hormone signaling, MiR-181a-5p
Original languageEnglish
Article number543
Number of pages19
JournalCancers
Volume13
Issue number3
Publication statusPublished - 2021
Publication categoryResearch
Peer-reviewedYes