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MicroRNAs (miRNAs) are a class of endogenously expressed non-coding regulators of the genome with an ability to mediate a variety of biological and pathological processes. There is growing evidence demonstrating frequent dysregulation of microRNAs in cancer cells, which is associated with tumor initiation, development, migration, invasion, resisting cell death, and drug resistance. Studies have shown that modulation of these small RNAs is a novel and promising therapeutic tool in the treatment of a variety of diseases, especially cancer, due to their broad influence on multiple cellular processes. However, suboptimal delivery of the appropriate miRNA to the cancer sites, quick degradation by nucleases in the blood circulation, and off target effects have limited their research and clinical applications. Therefore, there is a pressing need to improve the therapeutic efficacy of miRNA modulators, while at the same time reducing their toxicities. Several delivery vehicles for miRNA modulators have been shown to be effective in vitro and in vivo. In this review, we will discuss the role and importance of miRNAs in cancer and provide perspectives on currently available carriers for miRNA modulation. We will also summarize the challenges and prospects for the clinical translation of miRNA-based therapeutic strategies.


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Modulating microRNAs in cancer: next-generation therapies

Show Author's information Nahid Arghiani1,2Khalid Shah1,2,3 ( )
Center for Stem Cell and Translational Immunotherapy (CSTI), Harvard Medical School, Boston, MA 02115, USA
Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA

Abstract

MicroRNAs (miRNAs) are a class of endogenously expressed non-coding regulators of the genome with an ability to mediate a variety of biological and pathological processes. There is growing evidence demonstrating frequent dysregulation of microRNAs in cancer cells, which is associated with tumor initiation, development, migration, invasion, resisting cell death, and drug resistance. Studies have shown that modulation of these small RNAs is a novel and promising therapeutic tool in the treatment of a variety of diseases, especially cancer, due to their broad influence on multiple cellular processes. However, suboptimal delivery of the appropriate miRNA to the cancer sites, quick degradation by nucleases in the blood circulation, and off target effects have limited their research and clinical applications. Therefore, there is a pressing need to improve the therapeutic efficacy of miRNA modulators, while at the same time reducing their toxicities. Several delivery vehicles for miRNA modulators have been shown to be effective in vitro and in vivo. In this review, we will discuss the role and importance of miRNAs in cancer and provide perspectives on currently available carriers for miRNA modulation. We will also summarize the challenges and prospects for the clinical translation of miRNA-based therapeutic strategies.

Keywords: delivery systems, cancer therapy, MiRNAs, clinical translation, dysregulation

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Acknowledgements
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Publication history

Received: 13 May 2021
Accepted: 27 July 2021
Published: 15 March 2022
Issue date: March 2022

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©2022 Cancer Biology & Medicine.

Acknowledgements

This work was supported by NIH grants R01-CA201148 (K.S.) and by DoD grant LC180495.

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