YWHAG promotes the progression of lung adenocarcinoma through the JAK2/STAT3 pathway.

Abstract

YWHAG, also known as 14-3-3-γ, is one of the 14-3-3 isoforms. It can recognize phosphothreonine/phosphoserine residues and plays a critical role in regulating cellular metabolism, signal transduction, the cell cycle, and apoptosis. This study aims to elucidate the specific roles of YWHAG in Lung adenocarcinoma (LUAD). The mRNA expression of YWHAG was upregulated in LUAD and could serve as a potential predictive biomarker for prognosis and therapeutic efficacy, particularly in response to cisplatin, paclitaxel, docetaxel, and erlotinib. Additionally, the YWHAG protein was expressed at higher levels in LUAD tissues with poor differentiation and lymph node metastasis, and it was identified as an independent prognostic factor. Functional assays revealed that silencing YWHAG inhibited the proliferation and migration of lung cancer cells, while promoting apoptosis. Gene Set Enrichment Analysis (GSEA) identified that YWHAG was involved in several key pathways, including mTOR signaling, unfolded protein response, MYC targets and JAK/STAT3 signaling. Western blot analysis revealed that knockdown of YWHAG reduced the expression of p-JAK2 and p-STAT3. In conclusion, our findings suggest that YWHAG could serve as an attractive prognostic biomarker and a potential marker for drug response. Moreover, our study highlights that YWHAG exerts its oncogenic function through the JAK2/STAT3 signaling pathway, offering new insights into potential therapeutic strategies for LUAD.