ArticleBMC oral health2023
Coexpression network analysis identified MT3 as a hub gene that promotes the chemoresistance of oral cancer by regulating the expression of YAP1.
Article in BMC oral health, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Cadmium Exposure Facilitates Oral Squamous Cell Carcinoma Progression and Epithelial-mesenchymal Transition Through the Upregulation of ATP1B4.Biological trace element research · 2026Article
- A Protocol for Weighted Gene Co-expression Network Analysis With Module Preservation and Functional Enrichment Analysis for Tumor and Normal Transcriptomic Data.Bio-protocol · 2025Article
- Weighted gene co-expression network analysis reveals key stromal prognostic markers in pancreatic cancer.Scientific reports · 2024Article
- Epigenetic regulation of DNA repair gene program by Hippo/YAP1-TET1 axis mediates sorafenib resistance in HCC.Cellular and molecular life sciences : CMLS · 2024Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundOral cancer is considered one of the most malignant types of tumors and is known for its high likelihood of recurrence and metastasis. During clinical treatment, patients with oral cancer often develop resistance to chemotherapy, making the treatment process challenging. The purpose of this study was to investigate the genes related to chemotherapy resistance and their mechanisms in oral cancer patients.
methodsThe "limma" package was used to identify the differentially expressed genes between tumor and normal tissues from TCGA dataset. Subsequently, the "WGCNA" package was utilized to discover genes associated with chemoresistance. Cisplatin-resistant oral cancer cell lines were obtained through exposure to gradually increasing doses of cisplatin. SiRNA was used to knock down the MT3 and YAP1 genes to validate their functions. Finally, the therapeutic efficacy of combining a YAP1 inhibitor with cisplatin was confirmed by inoculating an oral cancer cell line in mice.
resultsIn our study, we analyzed 43 OSCC samples and identified 724 different genes using the weighted gene coexpression network analysis (WGCNA) method. Among these genes, MT3 stood out as strongly associated with chemotherapy resistance. Patients with high MT3 expression had worse prognoses, and MT3 levels were elevated in drug-resistant patients. Knocking down MT3 reversed tumor cell chemoresistance. We also observed that MT3 increased the expression of YAP1, potentially contributing to chemotherapy resistance by inducing tumor stemness through YAP1. In animal models, using YAP1 inhibitors improved the effectiveness of cisplatin in treating chemoresistant oral cancer.
conclusionsMT3 is related to chemotherapy resistance, which may be caused by its promotion of YAP1 expression and induction of tumor cell stemness. Inhibiting the activity of MT3 and YAP1 is helpful for increasing chemotherapy sensitivity.
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