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Published on: April 18, 2025
DNAJC5 promotes hepatocellular carcinoma cells proliferation though regulating SKP2 mediated p27 degradation
Hailong Wang1, Jiayu Luo1, Xuesi Tian1
1Center for Experimental Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China; Jiangxi Key Laboratory of Molecular Diagnostics and Precision Medicine, Nanchang, Jiangxi, China.
Abstract:
DNAJC5 (DnaJ heat shock protein family (Hsp40) member C5), also known as cysteine tandem protein (CSPα), is important for maintaining the normal function of nerve tissues, but its oncogenic function remains unknown. Here, we report a unique mechanism underlying the oncogenic function of DNAJC5. DNAJC5 protein expression is highly detectable in human hepatocellular carcinoma (HCC) tissues and is strongly related to a poor prognosis among HCC patients. DNAJC5 overexpression promotes HCC cell proliferation and reduced the ratio of cells in G1 phase of the cell cycle. Furthermore, DNAJC5 interacts with SKP2 and enhances the degradation of p27 (a cyclin-dependent kinase inhibitor1B) by promoting formation of the SKP2-p27 complex. In contrast, DNAJC5 knockdown rescues the SKP2-mediated decrease in p27 protein levels. These results reveal that the DNAJC5-SKP2-p27 pathway is a novel mechanism for the oncogenic function of DNAJC5 in HCC.
Insights
DNAJC5 protein promotes hepatocellular carcinoma (HCC) growth by interacting with SKP2 to degrade p27. This discovery reveals a new oncogenic mechanism for DNAJC5 in HCC, impacting patient prognosis.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- DNAJC5 (DnaJ heat shock protein family member C5), also known as cysteine tandem protein (CSPα), is crucial for nerve tissue function.
- The oncogenic role of DNAJC5 in cancer, particularly hepatocellular carcinoma (HCC), has not been previously established.
Purpose of the Study:
- To investigate the potential oncogenic function of DNAJC5 in hepatocellular carcinoma (HCC).
- To elucidate the molecular mechanism by which DNAJC5 contributes to HCC development and progression.
Main Methods:
- Analysis of DNAJC5 protein expression in human HCC tissues.
- Assessment of DNAJC5's effect on HCC cell proliferation and cell cycle.
- Investigation of the interaction between DNAJC5, SKP2, and p27 using molecular assays.
Main Results:
- DNAJC5 protein expression is elevated in HCC tissues and correlates with poor patient prognosis.
- Overexpression of DNAJC5 enhances HCC cell proliferation by promoting cell cycle progression from G1 phase.
- DNAJC5 interacts with SKP2, facilitating the degradation of p27 (a cyclin-dependent kinase inhibitor) and leading to decreased p27 protein levels.
Conclusions:
- The DNAJC5-SKP2-p27 signaling pathway represents a novel mechanism for DNAJC5's oncogenic activity in HCC.
- Targeting the DNAJC5-SKP2-p27 pathway may offer a therapeutic strategy for hepatocellular carcinoma.
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