S100A16 induces epithelial-mesenchymal transition in human PDAC cells and is a new therapeutic target for pancreatic cancer treatment that synergizes with gemcitabine
S100A16 induces epithelial-mesenchymal transition in human PDAC cells and is a new therapeutic target for pancreatic cancer treatment that synergizes with gemcitabine
复制标题
S100A16诱导人PDAC细胞上皮-间质转化，是与吉西他滨协同治疗胰腺癌的新治疗靶点
DOI：
10.1016/j.bcp.2020.114396
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发表时间：
2021-06-04
影响因子：
5.8
通讯作者：
Zeng, Linjuan
中科院分区：
文献类型：
--
作者：
Li, Ting;Ren, Tianyi;Zeng, Linjuan
胰腺导管腺癌 (PDAC) 是最致命的癌症之一，其 5 年生存率约为 6%，主要原因是治疗反应不佳和早期进展。 S100基因家族参与多种恶性肿瘤的多种病理生理过程。 S100A16是S100家族的成员，在PDAC中异常表达；然而，其生物学功能和作用机制仍不清楚。我们分析了基因表达综合 (GEO) 公共数据库和我们之前对与 M2 巨噬细胞共培养的人 PDAC 细胞系 PANC-1 的研究中收集的基因 ChIP 数据，以识别差异表达基因 (DEG)。通过筛选鉴定出二十三个过度表达的基因。然后，使用癌症基因组图谱（TCGA）数据库对所选基因进行分析，以评估它们是否对 PDAC 患者的总生存期（OS）有显着影响。在确定的 14 个 DEG 中，S100A16 与不良预后相关，被选择进行进一步研究；结果表明，TCGA数据集中S100A16与上皮间质转化（EMT）相关基因呈正相关。随后的体外和体内实验表明，S100A16诱导EMT促进人PDAC细胞的转移，并且该作用是通过增强TWIST1表达和激活STAT3信号通路介导的。吉西他滨 (GEM) 的抗肿瘤作用与 S100A16 下调结合增强。总之，我们的研究结果表明 S100A16 是人类 PDAC 治疗的一个新的潜在治疗靶点。
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a poor 5-year survival rate of approximately 6%, mostly due to poor treatment response and early progression. The S100 gene family participates in various pathophysiological processes in various malignancies. S100A16 is a member of the S100 family, which is abnormally expressed in PDAC; however, its biological functions and mechanisms of action remain unclear. We analysed the Gene Expression Omnibus (GEO) public database and the gene ChIP data collected in our previous study of human PDAC cell line PANC-1 cocultured with M2 macrophages to identify differentially expressed genes (DEGs). Twenty-three overexpressed genes were identified by screening. Then, the selected genes were analysed using The Cancer Genome Atlas (TCGA) database to assess whether they have significant impact on the overall survival (OS) of PDAC patients. Of the 14 DEGs identified, S100A16 was associated with poor prognosis and was selected for further investigation; the results indicate that S100A16 is positively correlated with epithelial-mesenchymal transition (EMT)-related genes in the TCGA dataset. Subsequent in vitro and in vivo experiments demonstrated that S100A16 induces the EMT to promote the metastasis of human PDAC cells and that the effect is mediated by the enhanced expression of TWIST1 and activation of the STAT3 signalling pathway. The antitumour effect of gemcitabine (GEM) was enhanced in combination with S100A16 downregulation. In conclusion, our findings suggest that S100A16 is a novel potential therapeutic target for human PDAC treatment.