CircPVT1 promotes ER-positive breast tumorigenesis and drug resistance by targeting ESR1 and MAVS.
Female
Humans
Breast Neoplasms
/ drug therapy
Carcinogenesis
/ genetics
Cell Line, Tumor
Cell Proliferation
Cell Transformation, Neoplastic
/ genetics
Drug Resistance, Neoplasm
/ genetics
Estrogen Receptor alpha
/ genetics
Gene Expression Regulation, Neoplastic
Tamoxifen
/ pharmacology
RNA, Circular
/ genetics
ERα
MAVS
anti-tumor immunity
breast cancer
circPVT1
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
15 05 2023
15 05 2023
Historique:
revised:
06
02
2023
received:
18
08
2022
accepted:
02
03
2023
medline:
16
5
2023
pubmed:
4
4
2023
entrez:
3
4
2023
Statut:
ppublish
Résumé
The molecular mechanisms underlying estrogen receptor (ER)-positive breast carcinogenesis and endocrine therapy resistance remain incompletely understood. Here, we report that circPVT1, a circular RNA generated from the lncRNA PVT1, is highly expressed in ERα-positive breast cancer cell lines and tumor samples and is functionally important in promoting ERα-positive breast tumorigenesis and endocrine therapy resistance. CircPVT1 acts as a competing endogenous RNA (ceRNA) to sponge miR-181a-2-3p, promoting the expression of ESR1 and downstream ERα-target genes and breast cancer cell growth. Furthermore, circPVT1 directly interacts with MAVS protein to disrupt the RIGI-MAVS complex formation, inhibiting type I interferon (IFN) signaling pathway and anti-tumor immunity. Anti-sense oligonucleotide (ASO)-targeting circPVT1 inhibits ERα-positive breast cancer cell and tumor growth, re-sensitizing tamoxifen-resistant ERα-positive breast cancer cells to tamoxifen treatment. Taken together, our data demonstrated that circPVT1 can work through both ceRNA and protein scaffolding mechanisms to promote cancer. Thus, circPVT1 may serve as a diagnostic biomarker and therapeutic target for ERα-positive breast cancer in the clinic.
Identifiants
pubmed: 37009655
doi: 10.15252/embj.2022112408
pmc: PMC10183818
doi:
Substances chimiques
Estrogen Receptor alpha
0
Tamoxifen
094ZI81Y45
RNA, Circular
0
ESR1 protein, human
0
MAVS protein, human
0
Banques de données
GEO
['GSE220776']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e112408Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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