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This study aims to identify C1orf226 as an oncogenic driver in glioma and its regulatory role in glioma stem cells.

June 19, 2026Cancer Medicine0 citationsOpen Access

C1orf226 Promotes Glioma Stemness and Oncogenesis in Glioma via PLK 1‐Mediated Wnt/β‐Catenin Signaling

YLYanbing LuZhoukou City Academy of Agricultural Sciences CJChao JiangHebei University of Economics and Business HWHongfei WuHainan General Hospital

Key Points

This study aims to identify C1orf226 as an oncogenic driver in glioma and its regulatory role in glioma stem cells.
Integrated three datasets for potential driver screening.
Conducted functional experiments on glioma cell proliferation, cell cycle, EMT, and apoptosis.
Used xenograft models to assess the impact of C1orf226 knockdown on tumor growth.
C1orf226 was significantly upregulated in glioma tissues compared to normal tissues, correlating with shorter survival.
C1orf226 promotes cell proliferation, EMT processes, and stemness while suppressing apoptosis in vitro.
C1orf226 knockdown restricted xenograft growth and reduced stemness markers; these effects were reversed by PLK1 co-expression.

Abstract

ABSTRACT Introduction Glioma stem cells (GSCs) are pivotal drivers of tumor progression and therapeutic resistance; however, the underlying regulatory mechanisms have not been fully elucidated. This study aimed to identify novel oncogenic drivers in glioma via a comprehensive multiomics analysis. Methods We integrated three datasets to screen potential oncogenic drivers. Functional experiments were performed to examine the effects of C1orf226 on glioma cell proliferation, cell cycle, epithelial–mesenchymal transition (EMT), and apoptosis. Additionally, tumor sphere formation assays, ALDH+/CD133+ cell detection, and stemness marker analysis were used to evaluate the role of C1orf226 in GSC stemness. Mechanistic studies involving immunoprecipitation (IP) and ubiquitination assays were applied to characterize the interaction between C1orf226 and PLK1, as well as their regulation on β‐catenin stability and Wnt/β‐catenin signaling. Rescue assays further verified the functional crosstalk between C1orf226 and PLK1. Xenograft mouse models were used in vivo to assess the impacts of C1orf226 knockdown on tumor growth and stemness markers. Results C1orf226 was significantly upregulated in glioma tissues compared with normal brain tissues. Its high expression correlated with shorter patient survival and served as an independent prognostic factor in the CGGA cohort. In vitro, C1orf226 exerted oncogenic function by facilitating cell proliferation, cell cycle progression, EMT‐like processes, and stemness, and suppressing apoptosis. Mechanistically, C1orf226 interacts with PLK1 to block its degradation, thereby activating PLK1 and downstream Wnt/β‐catenin signaling. Rescue experiments verified that PLK1 overexpression restored β‐catenin stability, Wnt/β‐catenin target gene expression, and GSC properties impaired by C1orf226 knockdown. In vivo, C1orf226 knockdown restrained xenograft growth and reduced stemness marker levels, and PLK1 co‐expression abrogated these effects. Conclusions Our findings reveal that C1orf226 is a PLK1‐dependent regulator of Wnt/β‐catenin signaling and GSC plasticity, highlighting its potential as a promising therapeutic target in glioma.

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