RCOR1 directly binds to MED28 and weakens its inducing effect on cancer stem cell-like activity of oral cavity squamous cell carcinoma cells

Background: Mediator is a multiprotein complex that acts as an essential transcriptional coactivator in eukaryotic cells for successful transcription. In this study, we aimed to explore the expression profile of 33 mediator subunit genes in oral cavity squamous cell carcinoma (OCSCC) and the functional role of MED28 in cellular behaviors of OCSCC cells.

Methods: Single-cell (sc)RNA-seq data from OCSCC cells (Puram 2017's dataset) and bulk-seq data of the OCSCC subgroup of TCGA-head and neck squamous cell carcinoma (HNSC) were used for bioinformatic analysis. SCC9 cells were used in in-vitro and in-vivo analysis.

Results: Among the 33 genes subjected to screening, MED28 showed the best prognostic value and its upregulation might independently predict shorter OS (HR: 3.699, 95% CI: 1.383-9.892, P = .009) and PFS (HR: 2.769, 95% CI: 1.462-5.244, P = .002). MED28 expression was positively correlated with cancer stem cell (CSC)-like properties of SCC9 cells, including colony/sphere formation, and the expression of CSC markers (CD44, KLF4, NANOG, and OCT4). RCOR1 could suppress the CSC-like properties of SCC9 cells and had direct interaction with MED28. Its overexpression partly abrogated MED28-induced expression of CSC markers. RCOR1 expression was associated with promoter hypermethylation, while MED28 expression was positively correlated with its MED28 copy number (Pearson's r = .44) in OCSCC tissues.

Conclusion: Among the mediator complex subunits, MED28 might serve as a potential biomarker of unfavorable survival. Its overexpression increased CSC-like activity of OCSCC cells, the effect of which could be abrogated by RCOR1 via direct interaction.