Inhibition of miR-10b treats metastatic breast cancer by targeting stem cell-like properties

Sep 21, 2026

Despite advances in breast cancer screening and treatment, metastatic disease has poor outcomes with low five-year survival, driven largely by therapies that fail to target metastatic-specific cellular properties. miR-10b, a noncoding RNA, promotes invasion, migration, viability, and proliferation, and can support stem cell-like traits linked to chemoresistance. This work develops MN-anti-miR10b to deliver anti-miR-10b antisense into cancer cells. In metastatic triple-negative mouse models, the nanodrug prevents metastasis onset and eliminates established metastases, including alongside chemotherapy. Transcriptomic evidence and expression data indicate miR-10b inhibition activates developmental programs and reduces stemness, identifying a strategy for stem-like breast cancer subtypes.

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CategoryHealthcare

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Abstract

Introduction

[www.oncotarget.com](www.oncotarget.com) Oncotarget, 2024, Vol. 15, pp: 591-606 Research Paper Inhibition of miR-10b treats metastatic breast cancer by targeting stem cell-like properties Alan Halim1, Nasreen Al-Qadi1, Elizabeth Kenyon1,2, Kayla N. Conner3,4, Sujan Kumar Mondal1,2, Zdravka Medarova5 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 4Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA 5Transcode Therapeutics Inc., Newton, MA 02458, USA Correspondence to: Anna Moore, [email](email: moorea57@msu.edu)[: moorea57@msu.edu](email: moorea57@msu.edu)[ ](email: moorea57@msu.edu)[Keywords](Keywords: breast cancer)[: breast cancer](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 ananodrug, termed MN-anti-miR10b, that delivers anti-miR-10b antisense oligomersto 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 celllike 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. INTRODUCTION Breast cancer is estimated to be the most diagnosed cancer overall and second-most lethal cancer among women in 2024 [1] . Changes to screening guidelines and advances in medicine have greatly increased survival rates; however, the most favorable prognoses are reserved for breast cancer detected when still localized, with a fiveyear survival rate of 99%[2] . Five-year survival rates for breast cancer that has metastasized to distant sites remain dismal at 30% overall [2] . A major contributor to this disparity in survival between localized and metastatic disease is the lack of therapeutics designed specifically for targeting metastases. Indeed, the breast cancer subtypes with the best survival rates – hormone receptor-positive or HER2-enriched – are those that are less likely to metastasize and with dependencies on signaling pathways that can be targeted therapeutically [2] . In contrast, metastatic disease is commonly of the triple-negative subtype, lacking a clear target and making treatment particularly difficult. While there is a need to

FAQs

What is miR-10b’s role in metastatic breast cancer according to the abstract?

miR-10b is implicated in cancer cell invasion, migration, viability, and proliferation, and is linked to stem cell-like properties associated with chemoresistance.

What therapeutic approach does the paper present?

It presents MN-anti-miR10b, a nanodrug that delivers anti-miR-10b antisense oligomers to cancer cells.

What outcomes were observed in metastatic mouse models?

In metastatic triple-negative breast cancer models, MN-anti-miR10b prevented the onset of metastasis and eliminated existing metastases, including in combination with chemotherapy after treatment stopped.

Sep 21, 2026

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