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Analyzing the mechanism by which oyster peptides target IL-2 in melanoma cell apoptosis based on RNA-seq and m6A-seq
Jiaojiao Han1,2, Lingxin Geng1,2, Chenyang Lu1,2
1State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Ningbo University, Ningbo, China. suxiurong_pub1ic@163.com.
Abstract:
Melanoma is a kind of skin cancer with high malignancy and strong proliferation and invasion abilities. Chemotherapy drugs in the clinic have the disadvantages of high price and high toxicity. Peptides are natural active ingredients that have many functions and are safe and effective. Previous studies have shown that oysters are rich in protein and have antitumor effects. In this study, a high-throughput strategy combined with MALDI TOF/TOF-MS and molecular docking was developed to screen peptides with antitumor functions from oyster hydrolysate. Three dominant peptides were predicted to have similar functions to IL-2 via molecular docking. Then, the activity of the peptides was confirmed in B16 cells, and we found that the three peptides increased the apoptosis of B16 cells. Furthermore, via RNA-seq and m6A-seq of B16 cells treated with the peptides, we found that ILADSAPR downregulates the expression of Pcna, Tlr4, and Ncbp2 and upregulates the expression of Bax, Bad, Pak4, Rasa2, Cct6, and Gbp2. ILADSAPR inhibited B16 cell proliferation and promoted cell apoptosis by regulating the expression of these genes. In addition, the result of metabolic pathway analysis also proved this point. This study provides a preliminary reference for antitumor research on oyster peptides.
Insights
Oyster-derived peptides show promise as a safe and effective melanoma treatment. One peptide, ILADSAPR, inhibited cancer cell proliferation and promoted apoptosis by regulating specific gene expressions.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Melanoma is a highly malignant skin cancer with limited treatment options.
- Current chemotherapy drugs are expensive and toxic.
- Oysters contain proteins with demonstrated antitumor properties.
Purpose of the Study:
- To screen and identify antitumor peptides from oyster hydrolysate.
- To investigate the mechanism of action of these peptides on melanoma cells.
Main Methods:
- High-throughput screening combined with MALDI TOF/TOF-MS.
- Molecular docking to predict peptide function.
- In vitro studies using B16 melanoma cells.
- RNA sequencing (RNA-seq) and m6A sequencing (m6A-seq) analysis.
Main Results:
- Three dominant peptides were identified with predicted IL-2-like functions.
- ILADSAPR significantly increased apoptosis in B16 cells.
- ILADSAPR regulated key genes involved in cell proliferation and apoptosis (e.g., Pcna, Bax, Bad).
Conclusions:
- Oyster peptides, particularly ILADSAPR, exhibit significant antitumor activity against melanoma.
- ILADSAPR functions by modulating gene expression related to cell cycle and apoptosis.
- This study offers a foundation for developing novel peptide-based melanoma therapies.
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