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Published on: January 7, 2019
Up-regulated deubiquitinase USP4 plays an oncogenic role in melanoma
Weinan Guo1, Jinyuan Ma1, Tianli Pei1
1Department of Dermatology, Xijing hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Abstract:
Melanoma is the most malignant skin cancer with increasing incidence worldwide. Although innovative therapies such as BRAF inhibitor and immune checkpoint inhibitor have gained remarkable advances, metastatic melanoma remains an incurable disease for its notorious aggressiveness. Therefore, further clarification of the underlying mechanism of melanoma pathogenesis is critical for the improvement of melanoma therapy. Ubiquitination is an important regulatory event for cancer hallmarks and melanoma development, and the deubiquitinating enzymes including ubiquitin-specific peptidase (USP) families are greatly implicated in modulating cancer biology. Herein, we first found that the expression of the deubiquitinase USP4 was significantly up-regulated in melanoma tissues and cell lines. Furthermore, although USP4 knockdown had little impact on melanoma cell proliferation, it could increase the sensitivity to DNA damage agent cisplatin. We subsequently showed that USP4 regulated cisplatin-induced cell apoptosis via p53 signalling. More importantly, USP4 could accentuate the invasive and migratory capacity of melanoma cells by promoting epithelial-mesenchymal transition. Altogether, our results demonstrate that the up-regulated USP4 plays an oncogenic role in melanoma by simultaneously suppressing stress-induced cell apoptosis and facilitating tumour metastasis.
Insights
Increased deubiquitinase USP4 expression promotes melanoma metastasis and reduces apoptosis sensitivity. Targeting USP4 may offer new therapeutic strategies for aggressive melanoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Melanoma is an aggressive skin cancer with increasing incidence and limited treatment options for metastatic disease.
- Ubiquitination, regulated by deubiquitinating enzymes like USP family members, plays a crucial role in cancer development.
- Understanding melanoma pathogenesis is vital for developing effective therapies.
Purpose of the Study:
- To investigate the role of deubiquitinase USP4 in melanoma pathogenesis.
- To explore USP4's impact on melanoma cell apoptosis and metastasis.
- To elucidate the molecular mechanisms underlying USP4's function in melanoma.
Main Methods:
- Analysis of USP4 expression in melanoma tissues and cell lines.
- Assessment of USP4 knockdown effects on melanoma cell proliferation and cisplatin sensitivity.
- Investigation of USP4's role in regulating p53 signaling and cisplatin-induced apoptosis.
- Evaluation of USP4's influence on melanoma cell invasion and migration, including epithelial-mesenchymal transition.
Main Results:
- USP4 expression was significantly upregulated in melanoma tissues and cell lines.
- USP4 knockdown increased melanoma cell sensitivity to cisplatin by regulating p53 signaling and apoptosis.
- USP4 knockdown did not significantly affect melanoma cell proliferation.
- USP4 overexpression enhanced melanoma cell invasion and migration by promoting epithelial-mesenchymal transition.
Conclusions:
- Upregulated USP4 acts as an oncogene in melanoma.
- USP4 suppresses stress-induced apoptosis and promotes tumor metastasis in melanoma.
- USP4 represents a potential therapeutic target for melanoma treatment.
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