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Cited by 15Cancer-related molecular mechanisms researchEstrogen and related hormone effectsEpigenetics and DNA Methylation

LncRNA PVT1 links estrogen receptor alpha and the polycomb repressive complex 2 in suppression of pro-apoptotic genes in hormone-responsive breast cancer

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Melone, Viola, Palumbo, Domenico, Palo, Luigi, Brusco, Noemi, Salvati, Annamaria, Tarallo, Antonietta, Giurato, Giorgio, Rizzo, Francesca +3 more·2025·Cell Death & Disease
DOI 10.1038/s41419-025-07423-4PMC PMC11807188
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Abstract

RNA-based therapeutics highlighted novel approaches to target either coding or noncoding molecules for multiple diseases treatment. In breast cancer (BC), a multitude of deregulated long noncoding RNAs (lncRNAs) have been identified as potential therapeutic targets also in the context of antiestrogen resistance, and the RNA binding activity of the estrogen receptor α (ERα) points additional potential candidates to interfere with estrogenic signaling. A set of lncRNAs was selected among ERα-associated RNAs in BC cell nuclei due to their roles in processes such as transcriptional regulation and epigenetic chromatin modifications. Native immunoprecipitation of nuclear ERα-interacting RNAs coupled to NGS (RIP-Seq) was performed in MCF-7 cells, leading to the identification of essential lncRNAs interacting with the receptor in multi-molecular regulatory complexes. Among these, PVT1, FGD5-AS1 and EPB41L4A-AS1 were selected for further investigation. Functional assays and transcriptome analysis following lncRNA knock-down indicated PVT1 as the master modulator of some of the most relevant BC hallmarks, such as cell proliferation, apoptosis, migration and response to hypoxia. In addition, targeted experiments identified PVT1 as a key factor in the composition of PRC2-ERα network involved in downregulation of tumor suppressor genes, including BTG2.

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  • Approximately 30% of ER+ breast cancer cases recur with resistance to Tamoxifen, and this recurrence can lead to more aggressive neoplasms.

    “Approximately 30% of ER+ breast cancer cases recur with resistance to Tamoxifen, and this recurrence can lead to more aggressive neoplasms23,24.”

    From Harnessing artificial intelligence to identify Bufalin as a molecular glue degrader of estrogen receptor alpha (2025) · cites this paper as [24]

    The Introduction (page unavailable) says that approximately 30% of patients with ERα-positive breast cancer acquire resistance to hormone therapies. It does not give that figure specifically for tamoxifen-resistant recurrence or say that recurrence leads to more aggressive neoplasms. (LLM, conf=0.87)

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References 55 · Cited by 15

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Authors
Melone, V., Palumbo, D., Palo, L., Brusco, N., Salvati, A., Tarallo, A., Giurato, G., Rizzo, F., Nassa, G., Weisz, A., & Tarallo, R.
Affiliations
  • University of Salerno (IT)
  • Telethon Institute Of Genetics And Medicine (IT)
Corresponding author
  • Weisz, Alessandro
  • Tarallo, Roberta
ORCID
Venue
Cell Death & Disease
Publisher
Springer Science and Business Media LLC
Published
2025-02-08
Volume
16
Issue
1
Pages
80-80
ISSN
2041-4889 (ISSN-L)
DOI
10.1038/s41419-025-07423-4
PMC
PMC11807188
OpenAlex
W4407266317
Cited by
15
References
55
Citations by year
2026: 8 · 2025: 7
FWCI
6.70
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Death and Disease (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Ministero dell'Istruzione, dell'Università e della Ricerca (2022A7HJEM, 202282CMEA, P2022N28FJ, 2022Y79PT4)
  • Ministero della Salute (GR-2021-12373937)
  • Associazione Italiana per la Ricerca sul Cancro (IG-23068)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
PVT1, long non-coding RNA, estrogen receptor alpha, polycomb repressive complex 2, hormone receptor-positive breast cancer, antiestrogen resistance, RIP-seq, FGD5-AS1, BTG2, tumor suppressor, apoptosis, cell proliferation, hypoxia response, cell migration, MCF-7 cells
MeSH terms
Breast Neoplasms, Cell Movement, Female, Humans, Gene Expression Regulation, Neoplastic, Apoptosis, Estrogen Receptor alpha, Cell Proliferation, MCF-7 Cells, RNA, Long Noncoding, Polycomb Repressive Complex 2

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