Background: Methyl-CpG-binding domain 2 (MBD2) attaches to methylated DNA, which mediates methylated gene transcription, leading to gene silencing and affecting tumor progression. The molecular mechanisms of MBD2 in head and neck squamous cell carcinoma (HNSCC) remain insufficiently characterized.
Aims: This study sought to assess the clinical relevance of MBD2 expression in HNSCC, with a particular focus on elucidating its functional role in tumor progression and its regulatory influence on p21 expression and cellular proliferation.
Methods: We analyzed the relationships between MBD2 expression, clinicopathological features, and survival outcomes in HNSCC patients using data from the UALCAN, TCGA, and cBioPortal databases. The functional role of MBD2 in HNSCC was further investigated through in vitro experiments. p21 expression was assessed using western blotting and qRT-PCR in TU212 and AMC-HN8 cells. These cells were treated with either shRNA targeting MBD2, 5-azacytidine (5-Aza), or a combination of shRNA MBD2 and 5-Aza. Additionally, cell proliferation and viability were measured in each treatment group.
Results: MBD2 was found to be frequently overexpressed in HNSCC tissues, and its altered expression was significantly associated with reduced overall survival (OS) and disease-free survival (DFS). Both shRNA-mediated MBD2 knockdown and 5-Aza treatment increased p21 expression in HNSCC cells, exhibiting similar functions with additive effects. Furthermore, both treatments significantly inhibited cell proliferation and viability.
Conclusion: These results indicated that shRNA-mediated MBD2 knockdown suppresses HNSCC cell growth by upregulating p21 expression. In addition to its role as an oncogene, MBD2 may serve as a prognostic biomarker and therapeutic target for HNSCC patients.
Keywords: 5‐azacytidine (5‐Aza); head and neck squamous cell carcinoma (HNSCC); methyl‐CpG‐binding domain 2 (MBD2); p21; prognosis.
© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.