Affiliation:
1. The Third Affiliated Hospital of Kunming Medical University: Yunnan Cancer Hospital
Abstract
Abstract
Background
Histone 3 lysine 4 methylation (H3K4me), especially histone 3 lysine 4 trimethylation (H3K4me3), is one of the most extensively studied patterns of histone modification and plays crucial roles in many biological processes. However, as a part of H3K4 methyltransferase that participates in H3K4 methylation and transcriptional regulation, retinoblastoma-binding protein 5 (RBBP5) has not been well studied in melanoma cancer. The present study sought to explore RBBP5-mediated H3K4 histone modification and the potential mechanisms in melanoma.
Methods
RBBP5 expression in melanoma and nevi specimens was detected by immunohistochemistry. Western blotting was performed for three pairs of melanoma cancer tissues and nevi tissues. In vitro and in vivo assays were used to investigate the function of RBBP5. The molecular mechanism was determined using RT-qPCR, western blotting, ChIP assays, and co-IP assays.
Results
Our study showed that RBBP5 was significantly downregulated in melanoma tissue and cells compared with nevi tissues and normal epithelia cells (P < 0.05). Reducing RBBP5 in human melanoma cells leads to H3K4me3 downregulation and promotes cell proliferation, migration, and invasion. On the one hand, we verified that WD repeat and SOCS box containing protein 2(WSB2) was an upstream gene of RBBP5-mediated H3K4 modification, which could directly bind to RBBP5 and negatively regulate its expression. On the other hand, we also confirmed that p16 (a cancer suppressor gene), was a downstream target of H3K4me3, the promoter of which can directly bind to H3K4me3. Mechanistically, our data revealed that RBBP5 inactivated the Wnt/β-catenin and epithelial-mesenchymal transition (EMT) pathways (P < 0.05), leading to melanoma suppression.
Conclusion
Histone methylation is rising as an important factor affecting tumorigenicity and tumour progression. Our findings verified the significance of RBBP5-mediated H3K4 modification in melanoma and the potential regulatory mechanisms of melanoma proliferation and growth, suggesting that RBBP5 is a potential therapeutic target for the treatment of melanoma.
Publisher
Research Square Platform LLC
Cited by
1 articles.
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