通过直接调控食管鳞状细胞癌中的表达促进肿瘤进展。
Facilitates Tumor Progression by Directly Regulating Expression in Esophageal Squamous Cell Carcinoma.
作者信息
Li Hongyi, Weng Yongjia, Wang Shaojie, Wang Fang, Wang Yanqiang, Kong Pengzhou, Zhang Ling, Cheng Caixia, Cui Heyang, Xu Enwei, Wei Shuqing, Guo Dinghe, Chen Fei, Bi Yanghui, Meng Yongsheng, Cheng Xiaolong, Cui Yongping
机构信息
Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, China.
Key Laboratory of Cellular Physiology, Ministry of Education, Shanxi Medical University, Taiyuan, China.
出版信息
Front Oncol. 2021 Oct 19;11:734655. doi: 10.3389/fonc.2021.734655. eCollection 2021.
BACKGROUND
is a copy number amplified gene identified not only in esophageal squamous cell carcinoma (ESCC) but also in various cancer types. Its clinical relevance and underlying mechanisms in ESCC have remained unknown.
METHODS
Tissue microarray data was used to analyze its expression in 179 ESCC samples. The effects of on proliferation, colony formation, and cell cycle were tested in ESCC cells. Real-time PCR and Western blot were used to detect the expression of its target genes. Correlation of with its target genes in ESCC and various SCC types was analyzed using GSE53625 and TCGA data. The mechanism of was studied by chromatin immunoprecipitation (ChIP), luciferase reporter assays, and rescue assay.
RESULTS
The overexpression of promoted proliferation, colony formation, and cell cycle in ESCC cells. affected the expression of cyclins in different cell phases. GSE53625 and TCGA data showed expression was positively correlated with . The knockdown of reversed the malignant phenotype induced by overexpression. Furthermore, was found to directly bind to , thus promoting its expression.
CONCLUSIONS
Our results reveal a novel mechanism of that it may act as an oncogene by directly upregulating to facilitate tumor progression in ESCC.
背景
是一种不仅在食管鳞状细胞癌（ESCC）中，而且在多种癌症类型中都被鉴定出的拷贝数扩增基因。其在ESCC中的临床相关性和潜在机制尚不清楚。
方法
利用组织微阵列数据分析其在179例ESCC样本中的表达。在ESCC细胞中检测其对增殖、集落形成和细胞周期的影响。采用实时PCR和蛋白质印迹法检测其靶基因的表达。利用GSE53625和TCGA数据，分析其在ESCC和各种SCC类型中与其靶基因的相关性。通过染色质免疫沉淀（ChIP）、荧光素酶报告基因检测和拯救实验研究其机制。
结果
的过表达促进了ESCC细胞的增殖、集落形成和细胞周期进程。影响了不同细胞周期时相中细胞周期蛋白的表达。GSE53625和TCGA数据显示，的表达与呈正相关。的敲低逆转了过表达诱导的恶性表型。此外，发现可直接与结合，从而促进其表达。
结论
我们的结果揭示了一种新的机制，即它可能通过直接上调来促进ESCC中的肿瘤进展，从而作为一种癌基因发挥作用。
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