RACK1 promotes NF-κB pathway activation and glioma cell proliferation by inhibiting RPS2 ubiquitination

Peng Cao1, Jun Tan1, Pinjing Zhang1

  • 1Department of Neurosurgery, General Hospital of Northern Theater Command, No.83 Wenhua Road,, Shenyang, Liaoning, 110840, China.

PubMed
Abstract

Insights

Receptor for Activated C Kinase 1 (RACK1) promotes glioma growth by stabilizing Ribosomal Protein S2 (RPS2), activating the NF-κB pathway. This interaction highlights RACK1 and RPS2 as potential therapeutic targets for aggressive brain tumors.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gliomas are aggressive brain tumors with a poor prognosis.
  • Receptor for Activated C Kinase 1 (RACK1) and Ribosomal Protein S2 (RPS2) are implicated in tumor progression.
  • The combined role of RACK1 and RPS2 in glioblastoma is not well understood.

Purpose of the Study:

  • To investigate the combined roles of RACK1 and RPS2 in glioblastoma.
  • To elucidate the molecular mechanisms by which RACK1 and RPS2 influence glioma progression.
  • To identify potential therapeutic targets for glioma.

Main Methods:

  • Bioinformatic analysis of glioma datasets (GSE41031, TCGA-glioma) to identify differentially expressed genes (DEGs) and perform protein-protein interaction (PPI) network analysis.
  • In vitro analysis of RACK1 and RPS2 expression and function in glioma cell lines.
  • Co-immunoprecipitation (Co-IP), ubiquitination assays, Western blotting, and luciferase reporter assays to investigate protein interactions, stability, and pathway activation (NF-κB).

Main Results:

  • RACK1 and RPS2 were identified as hub genes significantly upregulated in glioma and were associated with increased cell proliferation, migration, and invasion.
  • RACK1 knockdown induced G2/M phase cell cycle arrest by downregulating cyclin B1 and CDK1.
  • RACK1 stabilized RPS2 by inhibiting its ubiquitin-mediated degradation, thereby promoting the NF-κB pathway and glioma cell growth. Silencing RPS2 also inhibited proliferation.

Conclusions:

  • RACK1 promotes glioma cell proliferation and invasion by enhancing NF-κB pathway activation through the inhibition of RPS2 ubiquitination and degradation.
  • RACK1 and RPS2 represent potential biomarkers and therapeutic targets for glioma progression.

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