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

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.

Stress granules in cancer: Adaptive dynamics and therapeutic implications

“…The formation of SGs is anticipated to influence tumor biological responses in several significant ways, fundamentally reshaping how cancer cells react to diverse stress conditions and therapeutic interventions. Firstly, RBPs such as G3BP1/2, 63 , 64 TIA-1, 65 and FMRP 66 within SGs recognize specific RNA motifs and can alter the stability, localization, and translation of these mRNAs, which provides a new gene regulation perspective for cancer survival and proliferation. The second way is to limit the interaction of the separated components with the bulk cytosol.…”

“…Key component of SGs as G3BP1 engages with multiple signaling pathways, including the Wnt, TGF-β/Smad, and PI3K/Akt/mTORC1. 63 , 64 , 72 These signaling cascades are fundamental to the proliferation, invasion, and metastasis of tumor cells, highlighting G3BP1’s integral participation in the deregulated metabolism that supports cancer progression. Another study highlighted the role of G3BP1 in modulating the expression of G3BP2 and the involvement of post-translational modifications such as arginine methylation on G3BP2 at residue R468 by PRMT5.…”