Key points are not available for this paper at this time.
// Alan Halim 1 , Nasreen Al-Qadi 1 , Elizabeth Kenyon 1 , 2 , Kayla N. Conner 3 , 4 , Sujan Kumar Mondal 1 , 2 , Zdravka Medarova 5 and Anna Moore 1 , 2 1 Precision Health Program, Michigan State University, East Lansing, MI 48824, USA 2 Department of Radiology, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA 3 Department of Microbiology, Genetics, and Immunology, Michigan State University, East Lansing, MI 48824, USA 4 Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA 5 Transcode Therapeutics Inc., Newton, MA 02458, USA Correspondence to: Anna Moore, email: moorea57@msu.edu Keywords: breast cancer; metastasis; stem-like cells; nanoparticle; miR-10b Received: June 21, 2024 Accepted: August 13, 2024 Published: August 26, 2024 Copyright: © 2024 Halim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Despite advances in breast cancer screening and treatment, prognosis for metastatic disease remains dismal at 30% five-year survival. This is due, in large, to the failure of current therapeutics to target properties unique to metastatic cells. One of the drivers of metastasis is miR-10b, a small noncoding RNA implicated in cancer cell invasion, migration, viability, and proliferation. We have developed a nanodrug, termed MN-anti-miR10b, that delivers anti-miR-10b antisense oligomers to cancer cells. In mouse models of metastatic triple-negative breast cancer, MN-anti-miR10b has been shown to prevent onset of metastasis and eliminate existing metastases in combination with chemotherapy, even after treatment has been stopped. Recent studies have implicated miR-10b in conferring stem cell-like properties onto cancer cells, such as chemoresistance. In this study, we show transcriptional evidence that inhibition of miR-10b with MN-anti-miR10b activates developmental processes in cancer cells and that stem-like cancer cells have increased miR-10b expression. We then demonstrate that treatment of breast cancer cells with MN-anti-miR10b reduces their stemness, confirming that these properties make metastatic cells susceptible to the nanodrug actions. Collectively, these findings indicate that inhibition of miR-10b functions to impair breast cancer cell stemness, positioning MN-anti-miR10b as an effective treatment option for stem-like breast cancer subtypes.
Halim et al. (Mon,) studied this question.