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

靶向 microRNA-22 可抑制三阴性乳腺癌小鼠模型中的肿瘤扩散

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作者: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

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.

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