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

Abstract

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.

Wnt/β‐catenin signaling pathway participates in the effect of miR‐626 on oral squamous cell carcinoma by targeting RASSF4

“…The online software programs DIANA, miRDB, miRWalk, and TargetScan were used to predict the potential target genes of miR‐626, and 32 genes were shown as the predicted potential target genes (Figure 2A, Figure ). Eleven dysregulated genes were detected in OSCC tissues or cell lines, as reported by previous studies, including downregulated (RASSF4, 18 RCOR1, 24 DLG2 25 ) and upregulated genes (MEIS2, 26 MTDH, 6 DUSP4, 27 MFAP5, 28 KDM8, 29 NR4A3, 30 EYA4, 31 and FBXL5 32 ). MiRNAs have been widely reported to regulate gene expression by inhibiting translation and/or by inducing degradation of target genes 33 .…”

Single‐cell RNA sequencing in oral science: Current awareness and perspectives

“…of OSCC by scRNA-seq, upregulation of which was reported to increase the OSCC stem-cell like activity. 94 Seventy-four genes with significantly higher expression in breast cancer stem cells than in non-CSCs were identified by scRNA-seq, many of which were not markers of breast cancer, consistent with the idea that there is a shared expression profile among the CSCs from different cancers. 90 The identification of tumor stem cells by scRNA-seq may reveal the underlying mechanisms of tumor therapy resistance and tumor recurrence.…”

“…Using known markers of CSCs, 92 the presence of CSCs was validated in scRNA‐Seq data 93 . Mediator Complex Subunit 28 (MED28) was detected as DEG of OSCC by scRNA‐seq, upregulation of which was reported to increase the OSCC stem‐cell like activity 94 . Seventy‐four genes with significantly higher expression in breast cancer stem cells than in non‐CSCs were identified by scRNA‐seq, many of which were not markers of breast cancer, consistent with the idea that there is a shared expression profile among the CSCs from different cancers 90 .…”

Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response

“…[18][19][20] ), and tumor suppressor TFs GRHL1 and RCOR1 (ref. 21,22 ) in the tumor core (Extended Data Fig. 2b and Supplementary Table 3).…”