PreprintCited by 15RNA Research and SplicingCancer-related Molecular PathwaysSarcoma Diagnosis and Treatment

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The RNA binding proteins LARP4A and LARP4B promote sarcoma and carcinoma growth and metastasis

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Preprint — published as 10.1016/j.isci.2024.109288 · Paper page

Abstract

SUMMARY: RNA-binding proteins (RBPs) are emerging as important regulators of pathogenesis, including cancer. Here we reveal that the recently characterised RBPs LARP4A and LARP4B are differentially overexpressed in primary osteosarcoma and osteosarcoma lung metastases, as well as in prostate cancer. Depletion of LARP4A and LARP4B inhibited primary tumour growth and metastatic spread in xenograft studies, as well as inhibiting cell proliferation, motility and migration. Transcriptomic profiling combined with high content multiparametric cell cycle analysis unveiled a central role for LARP4B, but not LARP4A, in regulating cell cycle progression in osteosarcoma and prostate cancer cell lines, potentially through modulating the post-transcriptional regulation of RNA targets that include key cell cycle proteins such as Cyclins B1 and E2, Aurora B and E2F1. Our work assigns new functions to LARP4A and LARP4B as pro-tumorigenic proteins in bone and prostate cancer, highlights their similarities while indicating distinct functional aspects, and adds significantly to the rapidly increasing roles of RBPs in different cancer models. Uncovering clear biological roles for these paralogous proteins provides new avenues for identifying novel tissue-specific targets and potential druggable intervention.

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Metadata

Authors
Coleman, J. C., Tattersall, L., Yianni, V., Knight, L., Yu, H., Hallett, S., Johnson, P., Caetano, A., Cosstick, C., Ridley, A., Gartland, A., Conte, M. R., & Grigoriadis, A. E.
Affiliations
  • King's College London (GB)
  • University of Sheffield (GB)
  • University of Bristol (GB)
Corresponding author
  • Conte, Maria R
  • Grigoriadis, Agamemnon E.
Venue
iScience
Publisher
openRxiv
Published
2023-04-12
Volume
27
Issue
4
Pages
109288-109288
ISSN
2589-0042 (ISSN-L)
OpenAlex
W4392131697
Cited by
15
References
1
Citations by year
2026: 2 · 2025: 8 · 2024: 3 · 2023: 1
FWCI
1.75
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • iScience (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Research Portal (King's College London) (submittedVersion, cc-by)
Funders
  • King’s College London
  • Francis Crick Institute
  • King's College London (MR/N013700/1)
  • National Institutes of Health
  • Medical Research Council (MR/N013700/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Health Sciences › Medicine › Oncology › Sarcoma Diagnosis and Treatment
Keywords
LARP4B, RNA-binding proteins, osteosarcoma, prostate cancer, lung metastasis, tumor growth, cell cycle regulation, cyclin B1, cyclin E2, Aurora B kinase, E2F1, cell migration, cell proliferation, paralogous proteins

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