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Published on: February 1, 2020
Methylation status of the SOCS3 gene in human malignant melanomas
Tomoko Tokita1, Chihaya Maesawa, Toshimoto Kimura
1Department of Pathology, Iwate Medical University School of Medicine, Morioka 020-8505, Japan.
Abstract:
The suppressors of cytokine signaling (SOCS) family inhibits not only Janus kinase (JAK)/signal transducers and activators of transcription (STAT) but also focal adhesion kinase (FAK) signaling pathways, and has tumor suppressor activity. Aberrant methylation in the promoter region of the SOCS3 gene frequently occurs in several types of human malignancy, and its transcriptional silencing is associated with malignant tumor behavior. In malignant melanomas, the expression and methylation status of the SOCS3 gene have not been elucidated. We therefore examined the methylation status and/or protein expression of the SOCS3 gene in 5 human malignant melanoma cell lines, 2 primary cultures of normal melanocytes, and surgically resected tumors (5 malignant melanomas and 2 melanocytic nevi). Four of the 5 melanoma cell lines and the 2 primary cultures of normal melanocytes expressed SOCS3 protein to various degrees, and only one melanoma cell line was negative. Expression of SOCS3 protein was inversely correlated with methylation status in the SOCS3 promoter region, and treatment with a demethylating agent (5-aza-2'-deoxycytidine) was able to induce expression of the protein in one melanoma cell line that was SOCS3-negative and another that was weakly positive. Three of the 5 primary malignant melanomas and one of the 2 melanocytic nevi showed aberrant methylation. These results suggest that inactivation of the SOCS3 gene by hypermethylation may be involved in the promotion of malignant behavior of melanomas.
Insights
Suppressors of Cytokine Signaling 3 (SOCS3) gene inactivation by hypermethylation may promote malignant melanoma. SOCS3 protein expression was inversely correlated with promoter methylation in melanoma cells and tissues.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Suppressors of Cytokine Signaling (SOCS) proteins regulate key signaling pathways and possess tumor suppressor activity.
- Aberrant promoter methylation and transcriptional silencing of SOCS genes are linked to various human malignancies.
- The role of SOCS3 in malignant melanoma, specifically its expression and methylation status, remained largely uninvestigated.
Purpose of the Study:
- To investigate the methylation status and protein expression of the SOCS3 gene in malignant melanoma.
- To determine the correlation between SOCS3 gene methylation and its expression in melanoma.
- To explore the potential role of SOCS3 inactivation in melanoma progression.
Main Methods:
- Analysis of SOCS3 gene promoter methylation and protein expression in melanoma cell lines, normal melanocytes, and tumor tissues.
- Treatment of melanoma cell lines with a demethylating agent (5-aza-2'-deoxycytidine) to assess SOCS3 re-expression.
- Correlation analysis between methylation status and protein expression levels.
Main Results:
- SOCS3 protein was expressed in most melanoma cell lines and normal melanocytes, with inverse correlation to promoter methylation.
- Demethylating agent treatment induced SOCS3 expression in SOCS3-negative and weakly positive melanoma cell lines.
- Aberrant SOCS3 promoter methylation was observed in a significant proportion of primary malignant melanomas and melanocytic nevi.
Conclusions:
- Inactivation of the SOCS3 gene through hypermethylation is implicated in the malignant behavior of melanomas.
- SOCS3 may function as a tumor suppressor in melanoma, and its silencing via methylation is a potential mechanism for tumor promotion.
- These findings highlight SOCS3 as a potential therapeutic target in melanoma treatment.
