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Updated: Jun 6, 2025

Establishment of a Clinic-based Biorepository
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PRMT5/WDR77 Enhances the Proliferation of Squamous Cell Carcinoma via the ΔNp63α-p21 Axis

Heng Liang1,2, Matthew L Fisher1, Caizhi Wu1

  • 1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

Cancers
|November 27, 2024
PubMed

Insights

Protein arginine methyltransferase 5 (PRMT5) and WDR77 drive squamous cell carcinoma (SCC) growth by stabilizing ΔNp63α, inhibiting p21. Inhibiting PRMT5 and WDR77 offers a new therapeutic strategy for SCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Protein arginine methyltransferase 5 (PRMT5) is implicated in various cancers, but its role in squamous cell carcinoma (SCC) is understudied.
  • Understanding PRMT5's function in SCC is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the role of PRMT5 and its binding partner WDR77 in SCC proliferation.
  • To identify downstream targets and mechanisms by which PRMT5/WDR77 promotes SCC growth.

Main Methods:

  • Analysis of SCC patient data (TCGA, DepMap).
  • Cell proliferation assays (competition, MTT), flow cytometry, and in vivo mouse models.
  • Molecular analyses including single-cell RNA-seq, RT-qPCR, and Western blot.

Main Results:

  • Upregulation of PRMT5 and WDR77 correlates with poor survival in head and neck SCC (HNSCC) patients.
  • PRMT5/WDR77 stabilizes the ΔNp63α protein, which inhibits the cell cycle inhibitor p21, promoting SCC proliferation.
  • Depletion of PRMT5 and WDR77 suppressed SCC growth in vivo.

Conclusions:

  • PRMT5 and WDR77 synergistically promote SCC proliferation through the ΔNp63α-p21 pathway.
  • The PRMT5/WDR77 complex represents a novel therapeutic target for SCC treatment.
Keywords:
PRMT5WDR77cell proliferationp21squamous cell carcinomaΔNp63α

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