Glioma is an aggressive and malignant brain tumor with a poor prognosis, accounting for nearly half of all primary malignant brain tumors. Current treatments have limited efficacy and are often accompanied by side effects. Furthermore, the genetic diversity within glioma complicates the development of targeted therapies, warranting more research on the topic.

In a recent study published in the Genes & Diseases journal, researchers from University of Electronic Science and Technology of China, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and Sichuan University investigated the role of coiled-coil domain-containing protein 86 (CCDC86) in driving glioma progression.

The authors observed that CCDC86 was significantly upregulated in glioma tissues, showing a positive correlation with the patients' age, tumor recurrence, and pathological grade. Additionally, high expression of CCDC86 in gliomas was associated with poor overall survival, highlighting its potential as a prognostic marker for glioma.

Knockdown of CCDC86 suppressed the growth and migration of glioma cells, while enhancing their apoptosis. Further analysis of the downstream targets of CCDC86 identified ATF3 as its target gene; co-immunoprecipitation and nuclear fractionation assays indicated that CCDC86 stabilizes ATF3 transcription by interacting with BHLHE40. Subsequent experiments showed that ATF3 knockdown effectively inhibited the oncogenic effects of CCDC86 overexpression and reduced Ki67 expression. These findings collectively suggest that CCDC86 and ATF3 play crucial roles in regulating glioma growth, and that the interaction between CCDC86 and BHLHE40 contributes to glioma oncogenicity by stabilizing ATF3 transcription.

Additional experiments involving ATF3 knockdown, CCDC86 overexpression, or both ATF3 knockdown and CCDC86 overexpression revealed that overexpression of CCDC86 upregulates p-ERK and p-JNK1 levels, while ATF3 knockdown reversed this effect. Similarly, knockdown of ATF3 also reduced the expression of CCDC86, ATF3, ERK pathway-associated proteins & glycolysis-related proteins in the CCDC86 overexpression group.

Overall, the findings of this study establish that CCDC86, through ATF3, enhances glioma progression by regulating the ERK pathway and promoting aerobic glycolysis, which underscores its potential as a novel therapeutic target.

Reference

Title of the original paper: CCDC86-BHLHE40-ATF3 axis promotes aerobic glycolysis and tumor development in glioma

Journal: Genes & Diseases
Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch

DOI: https://doi.org/10.1016/j.gendis.2025.101643

Funding Information:

Key R&D Project of the Science and Technology Department of Sichuan Province, China (No. 2022YFS0146)

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.

Scopus Cite Score: 8.4 | Impact Factor: 9.4

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