RNA binding protein RBMS3 is a common EMT effector that modulates triple-negative breast cancer progression via stabilizing PRRX1 mRNA.
Animals
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Female
Gene Expression Regulation, Neoplastic
Homeodomain Proteins
/ chemistry
Humans
MCF-7 Cells
Mice
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Transplantation
RNA Stability
RNA-Binding Proteins
/ genetics
Trans-Activators
/ genetics
Triple Negative Breast Neoplasms
/ genetics
Up-Regulation
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
23
09
2020
accepted:
20
09
2021
revised:
08
09
2021
pubmed:
6
10
2021
medline:
31
12
2021
entrez:
5
10
2021
Statut:
ppublish
Résumé
The epithelial-to-mesenchymal transition (EMT) has been recognized as a driving force for tumor progression in breast cancer. Recently, our group identified the RNA Binding Motif Single Stranded Interacting Protein 3 (RBMS3) to be significantly associated with an EMT transcriptional program in breast cancer. Additional expression profiling demonstrated that RBMS3 was consistently upregulated by multiple EMT transcription factors and correlated with mesenchymal gene expression in breast cancer cell lines. Functionally, RBMS3 was sufficient to induce EMT in two immortalized mammary epithelial cell lines. In triple-negative breast cancer (TNBC) models, RBMS3 was necessary for maintaining the mesenchymal phenotype and invasion and migration in vitro. Loss of RBMS3 significantly impaired both tumor progression and spontaneous metastasis in vivo. Using a genome-wide approach to interrogate mRNA stability, we found that ectopic expression of RBMS3 upregulates many genes that are resistant to degradation following transcriptional blockade by actinomycin D (ACTD). Specifically, RBMS3 was shown to interact with the mRNA of EMT transcription factor PRRX1 and promote PRRX1 mRNA stability. PRRX1 is required for RBMS3-mediated EMT and is partially sufficient to rescue the effect of RBMS3 knockdown in TNBC cell lines. Together, this study identifies RBMS3 as a novel and common effector of EMT, which could be a promising therapeutic target for TNBC treatment.
Identifiants
pubmed: 34608266
doi: 10.1038/s41388-021-02030-x
pii: 10.1038/s41388-021-02030-x
pmc: PMC9421946
mid: NIHMS1828801
doi:
Substances chimiques
Homeodomain Proteins
0
PRRX1 protein, human
0
RBMS3 protein, human
0
RNA-Binding Proteins
0
Trans-Activators
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6430-6442Subventions
Organisme : NCI NIH HHS
ID : P30 CA022453
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009531
Pays : United States
Informations de copyright
© 2021. The Author(s), under exclusive licence to Springer Nature Limited.
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