Researcher ORCID Identifier

0000-0003-1296-2330

Graduation Year

2023

Date of Submission

12-2022

Document Type

Campus Only Senior Thesis

Degree Name

Bachelor of Arts

Department

Neuroscience

Reader 1

Emily Wiley

Reader 2

Scott Cooper

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Terms of Use for work posted in Scholarship@Claremont.

Rights Information

© YYYY Truman T Knowles

Abstract

Diffuse midline glioma (DMG) is the most lethal of all childhood cancers. DMGs are driven by histone tail mutation-mediated epigenetic dysregulation and partner mutations in genes controlling proliferation and migration. One result of this epigenetic and genetic landscape is the overexpression of LIN28B RNA binding protein. In other systems, LIN28B has been shown to prevent let-7 microRNA biogenesis; however, let-7, when available, faithfully suppresses cancer and induces cellular maturation by preventing the translation of numerous oncogenes. In this research proposal, an extensive review of literature on both LIN28A/B and all let-7 family members was performed across glioma subtypes. On the basis of this preliminary work, it was hypothesized that LIN28B is overexpressed and retains its canonical mechanism in DMG, resulting in an upregulation of let-7 targets. To investigate this hypothesis, two experimental aims are proposed. First, to measure LIN28B expression in a panel of DMG cell lines as a test of existing data. Second, to assess LIN28B localization in a panel of DMG patient samples as a test of its let-7-dependent mechanism. We then provide directions for future research into the timing and mechanisms behind LIN28B overexpression, as well as the mechanisms behind its localization. Finally, we offer that manipulation of the LIN28B/let-7 axis may induce therapeutic differentiation of DMG cells, thereby introducing a novel treatment modality to the field of pediatric neuro-oncology. Overall, this work paves the way for additional efforts to elucidate, and eventually target, LIN28B in DMG.

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