Deciphering the STAT3-PXN positive feedback loop in GBM, IDH-wildtype: transcriptional regulation and inhibition of YB-1 ubiquitination.

Overview

1. Department of Neurosurgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
2. Center of Brain Science, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
3. Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Ministry of Education, Shihezi University School of Medicine, Shihezi, China
4. Department of Pathophysiology, Shihezi University School of Medicine, Shihezi, China

Abstract

Glioblastoma (GBM) is the most fatal primary brain malignancy in adults, with a median survival of approximately 15 months. The 2021 WHO classification redefined GBM as exclusively IDH-wildtype based on its characteristic molecular and clinical features. In this study, we aimed to identify key prognostic genes in GBM, IDH-wildtype. Using univariate Cox proportional hazards regression analysis, PXN was identified as a critical upregulated gene in GBM, IDH-wildtype, significantly associated with poor prognosis. Its expression was further validated by qRT-PCR, western blotting, and immunohistochemistry. Functional assays revealed that elevated PXN enhances GBM malignancy, whereas its knockdown suppresses corresponding malignant features. Mechanistically, PXN and STAT3 form a positive feedback loop: STAT3 upregulates PXN transcription, and PXN, in turn, activates STAT3 by regulating SRC transcription. Additionally, PXN stabilizes YB-1 protein by inhibiting its ubiquitination. Further mRNA sequencing analysis demonstrated that YB-1 contributes to maintaining GBM malignancy through multiple signaling pathways. These results suggest that the STAT3-PXN positive feedback axis and the regulation of YB-1 stability by PXN may offer novel targets for GBM therapy.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• geo:GSE294052, at NCBI GEO; found in “Data availability”

Data availability

The data used in this study can be downloaded from TCGA dataset (https://xenabrowser.net/datapages/) and the CGGA dataset (http://www.cgga.org.cn). The mRNA sequencing data have been deposited in the Gene Expression Omnibus (GEO) under accession number GSE294052 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE294052). The R code used in this study is available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 7 authors, 2 keywords, 1 funder, 43 references.

Cite

This paper

Li, X., Guo, H., Liu, Z., Wang, T., Wang, M., Chen, W., & Yu, H. (2026). Deciphering the STAT3-PXN positive feedback loop in GBM, IDH-wildtype: transcriptional regulation and inhibition of YB-1 ubiquitination. Cell death discovery, 12(1), 168. https://doi.org/10.1038/s41420-026-03035-9

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