G3BP1 Interact with JAK2 mRNA to Promote the Malignant Progression of Nasopharyngeal Carcinoma via Activating JAK2/STAT3 Signaling Pathway

Int J Biol Sci. 2024 Jan 1;20(1):94-112. doi: 10.7150/ijbs.85341. eCollection 2024.

Abstract

Ras-GTPase-activating protein (GAP)-binding protein 1 (G3BP1) is an RNA-binding protein implicated in various malignancies. However, its role in nasopharyngeal carcinoma (NPC) remains elusive. This study elucidates the potential regulation mechanisms of G3BP1 and its significance in NPC advancement. Through knockdown and overexpression approaches, we validate G3BP1's oncogenic role by promoting proliferation, migration, and invasion in vitro and in vivo. Moreover, G3BP1 emerges as a key regulator of the JAK2/STAT3 signaling pathway, augmenting JAK2 expression via mRNA binding. Notably, epigallocatechin gallate (EGCG), a green tea-derived antioxidant, counteracts G3BP1-mediated pathway activation. Clinical analysis reveals heightened G3BP1, JAK2, and p-STAT3 as powerful prognostic markers, with G3BP1's expression standing as an independent indicator of poorer outcomes for NPC patients. In conclusion, the study unveils the oncogenic prowess of G3BP1, its orchestration of the JAK2/STAT3 signaling pathway, and its pivotal role in NPC progression.

Keywords: G3BP1; JAK2/STAT3 signaling pathway; RNA binding protein; malignant progression.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA Helicases* / metabolism
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Neoplasms* / genetics
  • Nasopharyngeal Neoplasms* / pathology
  • Poly-ADP-Ribose Binding Proteins / metabolism
  • RNA Helicases / genetics
  • RNA Helicases / metabolism
  • RNA Recognition Motif Proteins / genetics
  • RNA Recognition Motif Proteins / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / genetics

Substances

  • DNA Helicases
  • RNA Helicases
  • Poly-ADP-Ribose Binding Proteins
  • RNA Recognition Motif Proteins
  • STAT3 Transcription Factor
  • G3BP1 protein, human
  • JAK2 protein, human
  • Janus Kinase 2
  • STAT3 protein, human