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DNAJC9 promotes cervical cancer cell proliferation by regulating GLI1 expression.
Zhongyi Xie1,2, Longjiang Di1, Xingkai He1
1Institute of Gerontology, The First Affiliated Hospital of Shenzhen University; International Cancer Center, Guangdong Key Laboratory of Genome Instability and Human Disease Prevention, Marshall Laboratory of Biomedical Engineering, Department of Biochemistry and Molecular Biology, Shenzhen University Medical School, Shenzhen 518055, China.
Acta Biochimica Et Biophysica Sinica
|May 25, 2026
Summary
DNAJC9, a protein involved in histone regulation, drives cervical cancer growth by increasing GLI1. Inhibiting DNAJC9 may offer a new therapeutic strategy for cervical cancer.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- The role of DNAJC9 (a heat shock protein 40 family member) in cervical cancer is not well understood.
- DNAJC9 functions as a histone chaperone, influencing gene expression through epigenetic modifications.
Purpose of the Study:
- To investigate the role of DNAJC9 in cervical cancer progression.
- To identify downstream effectors and molecular mechanisms by which DNAJC9 influences cervical cancer cell proliferation and tumorigenicity.
Main Methods:
- Analysis of DNAJC9 expression in cervical cancer cell lines and clinical specimens.
- Functional studies involving DNAJC9 downregulation and GLI1 rescue experiments.
- Investigation of epigenetic mechanisms, including histone-protein interactions and histone acetylation at the GLI1 enhancer.
Main Results:
- DNAJC9 is overexpressed in malignant cervical cancer cells.
- Downregulation of DNAJC9 inhibits cancer cell proliferation, induces cell cycle arrest, and suppresses tumor formation.
- GLI1 was identified as a key downstream effector, with GLI1 restoration reversing the anti-proliferative effects of DNAJC9 inhibition.
- DNAJC9 facilitates GLI1 transcription by promoting p300-H3 interaction and sustaining H3K27ac at the GLI1 enhancer.
- A positive correlation between DNAJC9 and GLI1 expression was observed in clinical samples.
Conclusions:
- The DNAJC9-GLI1 axis plays a critical role in driving cervical cancer proliferation.
- DNAJC9 acts epigenetically to enhance GLI1 expression, promoting cervical cancer.
- The DNAJC9-GLI1 pathway represents a potential prognostic marker and therapeutic target for cervical cancer.
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