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

Riccardo Panella; Cody A Cotton; Valerie A Maymi; Sachem Best; Kelsey E Berry; Samuel Lee; Felipe Batalini; Ioannis S Vlachos; John G Clohessy; Sakari Kauppinen; Pier Paolo Pandolfi

doi:10.3390/biomedicines11051470

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

Biomedicines. 2023 May 18;11(5):1470. doi: 10.3390/biomedicines11051470.

Authors

Riccardo Panella^{1

2

3}, Cody A Cotton², Valerie A Maymi⁴, Sachem Best⁴, Kelsey E Berry², Samuel Lee⁴, Felipe Batalini^{1

5}, Ioannis S Vlachos^{1

5}, John G Clohessy^{1

4}, Sakari Kauppinen³, Pier Paolo Pandolfi^{1

6

7}

Affiliations

¹ Cancer Research Institute, Beth Israel Deaconess Cancer Center, Departments of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
² Center for Genomic Medicine, Desert Research Institute, Reno, NV 89512, USA.
³ Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, 2450 Copenhagen, Denmark.
⁴ Preclinical Murine Pharmacogenetics Facility and Mouse Hospital, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
⁵ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁶ Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, 10154 Turin, Italy.
⁷ Renown Institute for Cancer, Nevada System of Higher Education, Reno, NV 89502, USA.

Abstract

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.

Keywords: RNA medicine; breast cancer; microRNA.

Grants and funding

2019 BCRF/Breast Cancer Research Foundation