ZNF326 通过调节 ERCC1 的表达促进非小细胞肺癌细胞的增殖。
ZNF326 promotes proliferation of non-small cell lung cancer cells by regulating ERCC1 expression.
机构信息
Department of Pathology, College of Basic Medical Sciences and First Affiliated Hospital, China Medical University, Shenyang, PR China.
Neurosurgery, The First Affiliated Hospital, China Medical University, Shenyang, PR China.
出版信息
Lab Invest. 2019 Feb;99(2):169-179. doi: 10.1038/s41374-018-0148-y. Epub 2018 Nov 6.
The roles and downstream target genes of the transcription factor ZNF326 in malignant tumors are unclear. Out of 146 lung cancer tissue samples, we found that high expression of ZNF326 in 82 samples was closely related to low differentiation and a high pTNM stage of non-small cell lung cancer (NSCLC) cells. In vitro and in vivo analyses showed that ZNF326 significantly promoted cell cycle progression, colony formation, and proliferation as well as the growth of NSCLC transplanted tumors. Chromatin immunoprecipitation sequencing, dual-luciferase assay, and electrophoretic mobility shift assay confirmed that the C2H2 structure of ZNF326 binds to the -833 to -875 bp region of the ERCC1 promoter to initiate transcriptional activity. This binding promoted CyclinB1 synthesis and cell cycle progression. These results show that the ZNF326 transcription factor is highly expressed in lung cancer and promotes the proliferation of NSCLC cells by regulating the expression of ERCC1.
转录因子 ZNF326 在恶性肿瘤中的作用及其下游靶基因尚不清楚。在 146 例肺癌组织样本中，我们发现 82 例样本中 ZNF326 的高表达与非小细胞肺癌（NSCLC）细胞的低分化和高 pTNM 期密切相关。体外和体内分析表明，ZNF326 显著促进细胞周期进程、集落形成和增殖以及 NSCLC 移植瘤的生长。染色质免疫沉淀测序、双荧光素酶报告基因检测和电泳迁移率变动分析证实，ZNF326 的 C2H2 结构结合 ERCC1 启动子的-833 至-875bp 区域，启动转录活性。这种结合促进了 CyclinB1 的合成和细胞周期进程。这些结果表明，ZNF326 转录因子在肺癌中高表达，并通过调节 ERCC1 的表达促进 NSCLC 细胞的增殖。
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