Research Papers:
Inhibition of miR-10b treats metastatic breast cancer by targeting stem cell-like properties
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Abstract
Alan Halim1, Nasreen Al-Qadi1, Elizabeth Kenyon1,2, Kayla N. Conner3,4, Sujan Kumar Mondal1,2, Zdravka Medarova5 and Anna Moore1,2
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: | [email protected] |
Keywords: breast cancer; metastasis; stem-like cells; nanoparticle; miR-10b
Received: June 21, 2024 Accepted: August 13, 2024 Published: August 26, 2024
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.
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