Investigation of MANF regulation of glioma stemness via STAT3/TGF-β/SMAD4/p38 pathway based on pan-cancer analysis.

IF 4.1 2区医学 Q1 ONCOLOGY

Translational Oncology Pub Date : 2025-10-01 Epub Date: 2025-08-09 DOI:10.1016/j.tranon.2025.102497

Shi Feng, Ming Yang, Pengfei Dong, Fangfang Ding, Yang Hong, Huabao Cai, Xin Liu

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引用次数: 0

Abstract

Background: Glioma, particularly glioblastoma, is a highly aggressive brain tumor with poor prognosis and limited treatment options. Recent research highlights the role of MANF (Mesencephalic Astrocyte Derived Neurotrophic Factor) in tumor biology, yet its specific mechanisms in glioma remain underexplored. This study aims to elucidate the role of MANF in glioma and its underlying mechanisms of action.

Methods: We conducted bioinformatics analysis using TCGA data to identify MANF-related pathways, followed by cellular assays and subcutaneous tumor models for functional validation. Experiments included Western blot and qRT-PCR analysis to investigate the effects of MANF on glioma cell proliferation, migration, and stemness gene expression.

Results: MANF was found to be highly expressed in tumor tissues and associated with poor prognosis in glioma patients. Endogenous MANF regulates tumor cells by modulating the TGF-β/SMAD4/p38 pathway, promoting stemness and enhancing malignant behaviors, including migration and invasion. Exogenous MANF, however, did not significantly affect stemness gene expression but contributed to glioma cell proliferation.

Conclusions: MANF emerges as a promising therapeutic target for glioma. This study clarifies MANF's specific mechanisms, offering insights into its potential for targeted glioma therapies.

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基于泛癌分析的MANF通过STAT3/TGF-β/SMAD4/p38通路调控胶质瘤干细胞的研究

背景：胶质瘤，尤其是胶质母细胞瘤是一种高度侵袭性的脑肿瘤，预后差，治疗方案有限。最近的研究强调了MANF（中脑星形胶质细胞衍生神经营养因子）在肿瘤生物学中的作用，但其在胶质瘤中的具体机制仍未被充分探索。本研究旨在阐明MANF在胶质瘤中的作用及其潜在的作用机制。方法：我们使用TCGA数据进行生物信息学分析以确定manf相关通路，然后进行细胞分析和皮下肿瘤模型以进行功能验证。实验采用Western blot和qRT-PCR分析，探讨了MANF对胶质瘤细胞增殖、迁移和干细胞基因表达的影响。结果：在胶质瘤患者中，发现MANF在肿瘤组织中高表达并与预后不良相关。内源性MANF通过调节TGF-β/SMAD4/p38通路调控肿瘤细胞，促进肿瘤细胞的干性，增强肿瘤细胞的迁移和侵袭等恶性行为。然而，外源性MANF不显著影响干细胞基因的表达，但有助于胶质瘤细胞的增殖。结论：MANF有望成为胶质瘤的治疗靶点。这项研究阐明了MANF的特定机制，为其靶向胶质瘤治疗的潜力提供了见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology Biochemistry, Genetics and Molecular Biology-Cancer Research

CiteScore

7.20

自引率

2.00%

发文量

314

审稿时长

6-12 weeks

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.