Role of LIN28B in the Regulation of Ribosomal Biogenesis and Lipid Metabolism in Medulloblastoma Brain Cancer Cells

TL;DR

This study explores how LIN28B affects cell growth and metabolism in medulloblastoma, a type of aggressive pediatric brain cancer.

Contribution

The study reveals LIN28B's role in regulating ribosome biogenesis and lipid metabolism in medulloblastoma cells.

Findings

LIN28B silencing reduced medulloblastoma cell viability.

LIN28B knockdown impaired ribosome biogenesis and increased lipid accumulation.

Proteomics confirmed changes in protein expression linked to LIN28B.

Abstract

Background: Medulloblastoma (MB) is the most aggressive paediatric brain cancer, highlighting the urgent need for new diagnostic and prognostic biomarkers and improved treatments to enhance patient outcomes. Our previous study identified LIN28B, an RNA-binding protein, as a potential diagnostic and prognostic marker for MB and a pharmacological target to inhibit MB cell proliferation and stemness. However, the specific role of LIN28B and its mechanism of action in MB had not been studied. Methods: This study assessed LIN28B’s role in Daoy MB cells using siRNA-mediated silencing. LIN28B silencing was achieved with Dharmacon ON-TARGETplus SMARTpool and confirmed by Western blotting. Proliferation and protein assays evaluated the cell metabolic activity and viability. A proteomics analysis was conducted to examine the effect of LIN28B knockdown on the MB cell protein expression profile. The intracellular lipid droplets were assessed using the Nile Red Staining Kit, and nucleolar B23 protein levels were assessed by immunofluorescence. Both were visualised with a high-content IN Cell Analyser 2200. Results: Effective LIN28B silencing (>80%) was achieved in each experiment. LIN28B knockdown reduced the MB cell viability, impaired ribosome biogenesis, and promoted cellular lipid accumulation, as supported by proteomics and cell-based assays. Conclusions: This study highlights LIN28B as a promising target for regulating MB cell growth, ribosomal biogenesis, and lipid metabolism.

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