Abstract：Objective: To investigate the effect of lysine-specific demethylase 5 (KDM5A)-mediated trimethylation (H3K4me3) of lysine 4 of histone subunit III on the growth and metastasis of human oral squamous cell carcinoma (OSCC) cells and its mechanism. Methods: Human OSCC cell lines and human oral mucosal epithelial cells (HOMEC) were cultured, and the expression of KDM5A in the two cells was compared by RT-qPCR and Western blot. In the KDM5A knockdown assay, three groups, namely the control group, sh-NC group, and sh-KDM5A group, were established using the human OSCC cell line CAL27. Separately, in the KDM5A overexpression assay, another three groups, including the control group, oe-NC group, and oe-KDM5A group, were constructed with the same cell line. Lentiviral transfection was performed to achieve KDM5A knockdown or overexpression in CAL27 cells. The transfection efficiency was verified via reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot assays. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were conducted to evaluate the proliferative capacity of CAL27 cells, while the Transwell assay was employed to detect cell migration and invasion abilities. Western blot assay was used to determine the expression levels of E-cadherin and Vimentin in CAL27 cells. Additionally, Western blot assay was applied to measure the expression of p53 protein in KDM5A-knockdown CAL27 cells, and chromatin immunoprecipitation (ChIP)-qPCR was carried out to detect the enrichment levels of KDM5A and H3K4me2 in the p53 promoter region of CAL27 cells. Results: Compared with HOMEC, the relative expression levels of KDM5A mRNA and protein in human OSCC cell lines CAL27, HN30, HSC3 and SCC9 were upregulated (P<0.05). Compared with untransfected CAL27 cells and CAL27 cells transfected with sh-NC, the relative expression levels of KDM5A mRNA and protein in CAL27 cells transfected with sh-KDM5A were downregulated, the cell proliferation activity was decreased, the number of clones formed, the number of migration and the number of invasion were reduced, the relative expression level of E-cadherin protein was upregulated, and the relative expression level of Vimentin protein was downregulated (P<0.05). Compared with untransfected CAL27 cells and CAL27 cells transfected with oe-NC, the relative expression levels of KDM5A mRNA and protein in CAL27 cells transfected with oe-KDM5A was upregulated, the relative expression of mRNA and protein was upregulated, the cell proliferation activity was increased, the number of clones, migration and invasion were increased, the relative expression of E-cadherin protein was downregulated, and the relative expression of Vimentin protein was upregulated (P<0.05); in addition, the relative expression of p53 protein was upregulated in CAL27 cells transfected with sh-KDM5A, and the enrichment level of H3K4me3 in the p53 promoter region was increased (P<0.05). Conclusion: KDM5A promotes the growth and metastasis of human OSCC cells in vitro, and this mechanism may be related to its role in promoting H3K4me3 demethylation and subsequently inhibiting p53 expression.
王阳, 张玉梅, 娄茜萌, 张强. KDM5A介导的H3K4me3修饰对口腔鳞状细胞癌细胞生长和转移能力的影响[J]. 河北医学, 2026, 32(2): 189-197.
WANG Yang, et al. The Effect of KDM5A-Mediated H3K4me3 Modification on the Growth and Metastatic Capacity of Oral Squamous Cell Carcinoma Cells. HeBei Med, 2026, 32(2): 189-197.
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2026, Vol. 32 
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