Targeting of microRNA-22 Suppresses Tumor Spread in a Mouse Model of Triple-Negative Breast Cancer

microRNA-22 (miR-22) is an oncogenic miRNA whose up-regulation promotes epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis in hormone-responsive breast cancer. Here we show that miR-22 plays a key role in triple negative breast cancer (TNBC) by promoting EMT and aggressiveness i...

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Published inBiomedicines Vol. 11; no. 5; p. 1470
Main Authors Panella, Riccardo, Cotton, Cody A, Maymi, Valerie A, Best, Sachem, Berry, Kelsey E, Lee, Samuel, Batalini, Felipe, Vlachos, Ioannis S, Clohessy, John G, Kauppinen, Sakari, Pandolfi, Pier Paolo
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 18.05.2023
MDPI
Subjects
Analysis
Animal models
Antibodies
Breast cancer
Cell culture
Chemotherapy
Disease
Ethanol
Ethylenediaminetetraacetic acid
Metabolism
Metastases
Metastasis
MicroRNA
MicroRNAs
miRNA
Penicillin
Phosphatase
Proteins
RNA medicine
Statistical analysis
Tumors
Xenografts
RNA medicine
breast cancer
microRNA
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Summary:microRNA-22 (miR-22) is an oncogenic miRNA whose up-regulation promotes epithelial-mesenchymal transition (EMT), tumor invasion, and metastasis in hormone-responsive breast cancer. Here we show that miR-22 plays a key role in triple negative breast cancer (TNBC) by promoting EMT and aggressiveness in 2D and 3D cell models and a mouse xenograft model of human TNBC, respectively. Furthermore, we report that miR-22 inhibition using an LNA-modified antimiR-22 compound is effective in reducing EMT both in vitro and in vivo. Importantly, pharmacologic inhibition of miR-22 suppressed metastatic spread and markedly prolonged survival in mouse xenograft models of metastatic TNBC highlighting the potential of miR-22 silencing as a new therapeutic strategy for the treatment of TNBC.
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ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines11051470