Health Promotion Center, West China hospital, Sichuan University, Chengdu, China.
Tongren Municipal People's Hospital, Guizhou, China.
J Oral Pathol Med. 2021 Oct;50(9):882-890. doi: 10.1111/jop.13224. Epub 2021 Aug 25.
This study aimed to screen prognosis-related S100 protein family members in human paxpillomaviruses (HPV)-negative oral squamous cell carcinoma (OSCC) and their molecular regulations.
Bioinformatic screening was conducted based on single-cell RNA-seq data from Puram 2017 dataset and bulk-seq data from the Cancer Genome Atlas (TCGA). HPV-negative OSCC cell lines CAL-27 and SCC-4 were used as in vitro cell models.
Among 21 S100 protein family member genes, S100A13 upregulation was associated with unfavorable progression-free survival and disease-specific survival of OSCC patients. Gene Set Enrichment Analysis showed that the higher S100A13 expression group had elevated genes enriched in DNA repair and oxidative phosphorylation. S100A13 knockdown increased cisplatin sensitivity, while its overexpression decreased the sensitivity of CAL-27 and SCC-4 cells. S100A13 gene had complex alternative transcription patterns. ENST00000440685 is one of the major protein-coding transcripts and was the only transcript elevated in the tumor group. TEAD4 could bind to the promoter of ENST00000440685 and increase its transcription. TEAD4 overexpression alleviated the tumor-suppressive effect of cisplatin in terms of colony formation, the expression of apoptotic proteins, and DNA damage. However, S100A13 knockdown partly abrogated the protective effects of TEAD4 overexpression.
This study revealed a novel TEAD4-S100A13 axis that might modulate cisplatin sensitivity of OSCC tumor cells.
本研究旨在筛选人乳头瘤病毒（HPV）阴性口腔鳞状细胞癌（OSCC）中与预后相关的 S100 蛋白家族成员及其分子调控机制。
基于 Puram 2017 数据集的单细胞 RNA-seq 数据和癌症基因组图谱（TCGA）的批量-seq 数据进行生物信息学筛选。使用 HPV 阴性 OSCC 细胞系 CAL-27 和 SCC-4 作为体外细胞模型。
在 21 种 S100 蛋白家族成员基因中，S100A13 的上调与 OSCC 患者无进展生存期和疾病特异性生存期不良相关。基因集富集分析表明，S100A13 表达较高的组中，DNA 修复和氧化磷酸化相关的基因表达上调。S100A13 敲低增加了顺铂的敏感性，而过表达降低了 CAL-27 和 SCC-4 细胞的敏感性。S100A13 基因具有复杂的选择性转录模式。ENST00000440685 是主要的蛋白编码转录本之一，也是肿瘤组中唯一上调的转录本。TEAD4 可以结合到 ENST00000440685 的启动子上并增加其转录。TEAD4 的过表达在集落形成、凋亡蛋白表达和 DNA 损伤方面减轻了顺铂对肿瘤的抑制作用。然而，S100A13 的敲低部分削弱了 TEAD4 过表达的保护作用。
本研究揭示了一个新的 TEAD4-S100A13 轴，可能调节 OSCC 肿瘤细胞对顺铂的敏感性。
