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RPL41 inhibits the proliferation and migration of retinoblastoma through the ARL5B-associated lysosomal trafficking

Ye Li1, Tian Zhan1, Tianfu Chen1

  • 1Department of Ophthalmology, Shengjing Hospital of China Medical University, Shengyang, Liaoning, China.

Frontiers in Immunology
|December 26, 2025
PubMed
Abstract

Insights

Ribosomal protein L41 (RPL41) inhibits retinoblastoma growth and metastasis by degrading ATF4, which downregulates ARL5B and impairs lysosomal trafficking. This novel mechanism offers a potential therapeutic strategy for retinoblastoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Retinoblastoma is a common pediatric intraocular cancer with high metastatic potential.
  • Ribosomal protein L41 (RPL41) exhibits in vitro antitumor activity by promoting ATF4 degradation.

Purpose of the Study:

  • To evaluate the therapeutic efficacy of RPL41 in retinoblastoma.
  • To elucidate the underlying molecular mechanisms of RPL41's action, focusing on ATF4 and ARL5B.

Main Methods:

  • Construction of a xenografted retinoblastoma mouse model for in vivo evaluation.
  • Utilized mass spectrometry, qRT-PCR, Western blotting, and immunohistochemistry to assess gene and protein expression.
  • Employed chromatin immunoprecipitation (ChIP) and luciferase reporter assays to investigate ATF4-ARL5B interactions.

Main Results:

  • RPL41 inhibited retinoblastoma xenograft growth and reduced ARL5B expression in retinoblastoma cells.
  • ARL5B was found to be upregulated in retinoblastoma tissues.
  • RPL41 treatment led to ATF4 degradation, subsequently decreasing ARL5B and lysotransfer-related molecule levels, with ATF4 positively regulating ARL5B.

Conclusions:

  • RPL41 downregulates ARL5B expression via ATF4 degradation.
  • Impaired ARL5B-related lysosomal trafficking is a key mechanism by which RPL41 inhibits retinoblastoma metastasis.
Keywords:
ARL5BATF4RPL41lysosomal functionmetastasisretinoblastoma

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