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Isolation, Enrichment, and Maintenance of Medulloblastoma Stem Cells
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LIN28 expression and function in medulloblastoma.

Ahmed Maklad1, Mohammed Sedeeq1, Richard Wilson2

  • 1School of Pharmacy and Pharmacology, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia.

Journal of Cellular Physiology
|January 17, 2023
PubMed
Summary
This summary is machine-generated.

LIN28B is upregulated in medulloblastoma (MB), a pediatric brain tumor, and may serve as a diagnostic marker. Inhibiting LIN28 reduced MB cell growth and stemness, suggesting it as a potential therapeutic target.

Keywords:
LIN28ALIN28Bbiomarkermedulloblastomaproliferationstemness

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Area of Science:

  • Oncology
  • Molecular Biology
  • Pediatric Neuro-oncology

Background:

  • Medulloblastoma (MB) is the most common malignant pediatric brain tumor with suboptimal treatments and significant adverse effects.
  • Improved diagnostic and prognostic biomarkers are crucial for enhancing MB patient therapy outcomes.
  • RNA-binding proteins LIN28A and LIN28B regulate cancer invasiveness, but their role in MB was previously unstudied.

Purpose of the Study:

  • To investigate the expression and function of LIN28A and LIN28B in medulloblastoma.
  • To assess the impact of LIN28 inhibition on MB cell growth, metabolism, and stemness.
  • To evaluate LIN28B as a potential diagnostic/prognostic marker and therapeutic target for MB.

Main Methods:

  • Quantified LIN28A and LIN28B expression in MB patient tissues and cell lines.
  • Utilized pharmacological inhibition of LIN28 activity in MB cell lines (D283, CHLA-01R).
  • Assessed effects on cell growth, intracellular ATP levels, stemness marker (CD133) expression, and sphere formation.

Main Results:

  • LIN28B was significantly upregulated in MB tissues compared to normal brain tissue, specifically in aggressive subgroups, correlating with survival and metastasis.
  • Pharmacological inhibition of LIN28 reduced LIN28B expression and MB cell growth in a concentration-dependent manner.
  • LIN28 inhibition decreased CD133 expression and sphere formation, indicating reduced stemness, without affecting ATP levels.

Conclusions:

  • LIN28B is a potential diagnostic and prognostic biomarker for medulloblastoma.
  • LIN28 inhibition demonstrates potential as a therapeutic strategy to suppress MB cell growth and stemness.
  • Further research into LIN28 as a therapeutic target for MB is warranted.