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

Benedetti, Rosaria ; Papulino, Chiara ; Sgueglia, Giulia ; Chianese, Ugo ; De Marchi, Tommaso LU ; Iovino, Francesco ; Rotili, Dante ; Mai, Antonello ; Niméus, Emma LU and Aversana, Carmela Dell’ , et al. (2021) In Cancers 13(3).
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Breast cancer, Endocrine therapy, Epigenetic SERD, ERα, Hormone signaling, MiR-181a-5p
in
Cancers
volume
13
issue
3
article number
543
pages
19 pages
publisher
Multidisciplinary Digital Publishing Institute (MDPI)
external identifiers
  • pmid:33535487
  • scopus:85100578967
ISSN
2072-6694
DOI
10.3390/cancers13030543
language
English
LU publication?
yes
id
05028db5-ae6c-4ba7-bbb8-d1a8c41202a0
date added to LUP
2021-02-23 09:39:07
date last changed
2021-02-24 03:00:04
@article{05028db5-ae6c-4ba7-bbb8-d1a8c41202a0,
  abstract     = {<p>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.</p>},
  author       = {Benedetti, Rosaria and Papulino, Chiara and Sgueglia, Giulia and Chianese, Ugo and De Marchi, Tommaso and Iovino, Francesco and Rotili, Dante and Mai, Antonello and Niméus, Emma and Aversana, Carmela Dell’ and Altucci, Lucia},
  issn         = {2072-6694},
  language     = {eng},
  number       = {3},
  publisher    = {Multidisciplinary Digital Publishing Institute (MDPI)},
  series       = {Cancers},
  title        = {Regulatory interplay between mir-181a-5p and estrogen receptor signaling cascade in breast cancer},
  url          = {http://dx.doi.org/10.3390/cancers13030543},
  doi          = {10.3390/cancers13030543},
  volume       = {13},
  year         = {2021},
}