Tumor Suppressor microRNAs as Potential Treatment Therapeutics for Advanced Medulloblastoma

Authors

  • Chanlee Luu Department of Biotechnology, Virginia Western Community College, Roanoke, VA, USA; Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA
  • Gabriel Salyer Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA; Department of Biology, New College of Florida, FL, USA
  • Linda Gerace Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA; Department of English, Southern New Hampshire University, Manchester, NH, USA
  • Maryam Abdul-Kader Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA; Department of Biomedical Engineering, University of Illinois at Chicago, Chicago, IL, USA
  • Ava Azizi Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA; Department of Biological Science, Illinois Institute of Technology, Chicago, IL, USA
  • Alan Mariño del Puerto Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA; College of Natural Sciences, Minerva University, San Francisco, CA, USA
  • Param Thakkar Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA; Department of Biology, Loyola University Chicago, Chicago, IL, USA
  • Yvonne Chen Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA; Department of Biology, Brandeis University, Waltham, MA, USA
  • Jill Ivory Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA; Department of Biology, Grove City College, Grove City, PA, USA
  • Rebecca Amrick Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA; Department of English, Villanova University, Villanova, PA, USA
  • Martina Novajas Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA; Department of Biology, Oberlin College and Conservatory, Oberlin, OH, USA
  • Evan Schnieder Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA; Department of Informatics, Northern Kentucky University, Highland Heights, KY, USA
  • Brian D. Adams Department of RNA Sciences, The Brain Institute of America, New Haven, CT, USA

DOI:

https://doi.org/10.62382/jcbt.v2i1.31

Keywords:

miRNA, ncRNA, Therapy, Cancer, Medulloblastoma, Tumor suppressor, Neurology

Abstract

Medulloblastoma (MB) is one of the most prevalent forms of malignant brain cancer observed within pediatric patients and is particularly difficult to diagnose and treat due to the anatomical localization of tumors near the brainstem. Currently, there are four molecular classifications of MBL: WNT, SHH, Group 3, and Group 4 tumor subgroups. Wingless-type (WNT) mutant tumors are the least common, often caused by mutations in the CTNNB1 gene that plays a crucial role in the wingless cell signaling pathway, yet associates with the best prognosis as compared to all other MBL subtypes. Sonic hedgehog (SHH) mutant tumors arise due to continued release of Shh from purkinje cells, and an uninhibited proliferation response by granular neuronal precursors (GNPs). Group 3 and 4 MBL subgroups are still a molecularly heterogeneous class of tumors, with Group 3 MBL being highly associated with metastasis upon diagnosis, and more prevalently characterized by MYC amplification and activation. Group 4 MBL tumors comprise approximately 40% of all MBL, and remain remarkably heterogeneous with respect to somatic mutations of genes such as KDM6A, OTX2, ZMYM3, with an approximate 80% of tumors harboring chromosome 17 copy number alterations. While a majority of MBL cases cannot be linked to a single protein coding gene alteration, the role of non-coding RNAs, such as miRNAs, seems quite promising as a genetic marker to further sub-categorize MBL at the molecular level. Furthermore, miRNA-based therapy is proving to be a promising treatment to curb the growth of a number of cancer types within the clinic, with particular miRNAs under investigation including miR-34a, miR-211, and miR-584-5p. These miRNAs are known to induce cell cycle arrest in mouse models and demonstrate anti-tumorigenic properties in vitro, meriting further investigation of miRNA-based clinical trials for pediatric MBL patients.

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Published

2025-01-01

How to Cite

Luu, C., Salyer, G., Gerace, L., Abdul-Kader, M., Azizi, A., Puerto, A. M. del, … Adams, B. D. (2025). Tumor Suppressor microRNAs as Potential Treatment Therapeutics for Advanced Medulloblastoma. Journal of Cancer Biomoleculars and Therapeutics, 2(1), 45–56. https://doi.org/10.62382/jcbt.v2i1.31

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Vol. 2 No. 1 (2025)

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