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POFUT1 Serves as an Independent Prognostic Factor and Therapeutic Target by Activating the PI3K/AKT Pathway in Glioma.

Overview

Authors: Kai Yang1, Chunlei Ju1, Yifan Wang2, Aijie Guo1, Xiaochen Yang1, Yang Mi1, Yifei Su1, Chunhong Wang1, Hongming Ji1
  1. Department of Neurosurgery, Shanxi Provincial People's Hospital, Shanxi Medical University, Taiyuan, China
  2. The Neurosurgery Department, Xi'an Xidian Hospital, Xi'an, China
Journal: Brain and behavior, volume 16, issue 9, article e71701
Dates: received 21 January 2026; accepted 4 August 2026; published online 31 August 2026; in print September 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/brb3.71701 · PMID 42675310 · PMCID PMC13529811 · OpenAlex W7204772209
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: genetics / omics (modality), human (organism), mouse (organism), other condition (population), clinical / translational (subfield)
Methods: Statistics, Connectivity
Keywords: glioma, PI3K, POFUT1, prognosis
MeSH: Brain Neoplasms*, Fucosyltransferases*, Glioma*, Phosphatidylinositol 3-Kinases*, Proto-Oncogene Proteins c-akt*, Animals, Cell Line, Tumor, Cell Movement, Cell Proliferation, Female, Humans, Male, Mice, Prognosis, Signal Transduction (* major topic)
Topic: Glioma Diagnosis and Treatment (Genetics, Medicine), according to OpenAlex
Funding: Shanxi Provincial Collaborative Project on Integrated Traditional Chinese and Western Medicine for Major and Complex Diseases; Fundamental Research Program of Shanxi Province (202203021222362,202403021211136); Central Government Guiding Fund for Local Science and Technology Development Projects
Citations: not cited yet (Europe PMC); 24 references in the paper

Abstract

Objective: Protein O‐fucosyltransferase 1 (POFUT1) has been implicated in several malignancies, but its functional and prognostic significance in glioma remains insufficiently defined. This study evaluated whether POFUT1 expression is associated with glioma progression, patient outcome, and PI3K/AKT pathway activity.

Methods: Public glioma transcriptome datasets from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) were analyzed and compared with clinical samples collected from 123 glioma patients. POFUT1 protein levels in clinical specimens were determined by immunohistochemical staining, and its association with patient outcome was analyzed using survival curves. In vitro, glioma cell growth, motility, and invasiveness were examined using MTT and Transwell assays. The effect of POFUT1 on tumor formation was further tested in a subcutaneous xenograft model. RNA sequencing, KEGG pathway enrichment, and pharmacological inhibition were then used to explore the mechanism linking POFUT1 to PI3K/AKT signaling.

Results: POFUT1 expression was higher in glioma than in normal brain tissue and increased with tumor grade. Patients with high POFUT1 levels had shorter overall survival, and multivariate Cox analyses supported POFUT1 as an independent prognostic indicator. Incorporating POFUT1 into a nomogram improved prediction of 1‐, 3‐, and 5‐year survival. Functionally, POFUT1 knockdown reduced glioma cell growth, motility, invasion, and xenograft expansion, whereas POFUT1 overexpression produced the opposite phenotype. Transcriptomic and protein analyses indicated that POFUT1 enhanced PI3K/AKT signaling. The PI3K inhibitor LY294002 weakened the tumor‐promoting effects caused by POFUT1 overexpression.

Conclusion: POFUT1 as a key driver of glioma malignancy, predominantly through activating the PI3K‐AKT signaling pathway. These findings highlight POFUT1 as a promising novel therapeutic target for aggressive glioma.

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

Code

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Data

Datasets cited

Data Availability Statement

The transcriptomic sequencing data obtained from this study have been archived in the GEO repository and can be accessed using the accession ID GSE316535 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316535).

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

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 4 keywords, 15 MeSH terms, 3 funders, 24 references.

Cite

This paper

Yang, K., Ju, C., Wang, Y., Guo, A., Yang, X., Mi, Y., Su, Y., Wang, C., & Ji, H. (2026). POFUT1 Serves as an Independent Prognostic Factor and Therapeutic Target by Activating the PI3K/AKT Pathway in Glioma. Brain and behavior, 16(9), e71701. https://doi.org/10.1002/brb3.71701

BibTeX

@article{yang2026pofut1,
author = {Yang, Kai and Ju, Chunlei and Wang, Yifan and Guo, Aijie and Yang, Xiaochen and Mi, Yang and Su, Yifei and Wang, Chunhong and Ji, Hongming},
title = {{POFUT1 Serves as an Independent Prognostic Factor and Therapeutic Target by Activating the PI3K/AKT Pathway in Glioma}},
journal = {Brain and behavior},
year = {2026},
month = sep,
volume = {16},
number = {9},
pages = {e71701},
publisher = {Wiley},
issn = {2162-3279},
doi = {10.1002/brb3.71701},
url = {https://doi.org/10.1002/brb3.71701},
pmid = {42675310},
pmcid = {PMC13529811}
}

RIS

TY - JOUR
AU - Yang, Kai
AU - Ju, Chunlei
AU - Wang, Yifan
AU - Guo, Aijie
AU - Yang, Xiaochen
AU - Mi, Yang
AU - Su, Yifei
AU - Wang, Chunhong
AU - Ji, Hongming
TI - POFUT1 Serves as an Independent Prognostic Factor and Therapeutic Target by Activating the PI3K/AKT Pathway in Glioma
T2 - Brain and behavior
J2 - Brain Behav
PY - 2026
DA - 2026/09/01
VL - 16
IS - 9
SP - e71701
SN - 2162-3279
PB - Wiley
DO - 10.1002/brb3.71701
UR - https://doi.org/10.1002/brb3.71701
LA - en
ER -

CSL-JSON

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