Department of Oral and Maxillofacial Surgery, Second Affiliated Hospital of Army Military Medical University, Chongqing, China.
Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
J Oral Pathol Med. 2020 Sep;49(8):741-750. doi: 10.1111/jop.13022. Epub 2020 May 14.
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.
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.
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.
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.
介体是一种多蛋白复合物，作为真核细胞中成功转录的必需转录共激活因子发挥作用。在这项研究中，我们旨在探索 33 种介体亚基基因在口腔鳞状细胞癌（OCSCC）中的表达谱，以及 MED28 在 OCSCC 细胞的细胞行为中的功能作用。
使用来自 OCSCC 细胞的单细胞（sc）RNA-seq 数据（Puram 2017 的数据集）和 TCGA-头颈部鳞状细胞癌（HNSC）的 OCSCC 亚组的 bulk-seq 数据进行生物信息学分析。SCC9 细胞用于体外和体内分析。
在筛选的 33 个基因中，MED28 显示出最佳的预后价值，其上调可能独立预测较短的总生存期（HR：3.699，95%CI：1.383-9.892，P=0.009）和无进展生存期（HR：2.769，95%CI：1.462-5.244，P=0.002）。MED28 的表达与 SCC9 细胞的癌症干细胞（CSC）样特性呈正相关，包括集落/球体形成以及 CSC 标志物（CD44、KLF4、NANOG 和 OCT4）的表达。RCOR1 可以抑制 SCC9 细胞的 CSC 样特性，并且与 MED28 具有直接相互作用。其过表达部分消除了 MED28 诱导的 CSC 标志物表达。RCOR1 的表达与启动子过度甲基化相关，而 MED28 的表达与 OCSCC 组织中 MED28 拷贝数呈正相关（Pearson's r=0.44）。
在介体复合物亚基中，MED28 可能是不利生存的潜在生物标志物。其过表达增加了 OCSCC 细胞的 CSC 样活性，RCOR1 通过直接相互作用可以消除其作用。
