ZNF326 promotes proliferation of non-small cell lung cancer cells by regulating ERCC1 expression
ZNF326 promotes proliferation of non-small cell lung cancer cells by regulating ERCC1 expression
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ZNF326通过调节ERCC1表达促进非小细胞肺癌细胞增殖
DOI：
10.1038/s41374-018-0148-y
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发表时间：
2019
影响因子：
5
通讯作者：
Wang Enhua
中科院分区：
文献类型：
--
作者：
Wu Jingjing;Zhang Xiupeng;Han Qiang;Han Xu;Rong Xuezhu;Wang Minghao;Zheng Xiaoying;Wang Enhua
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份肺癌组织样本中，我们发现82份样本中ZNF326的高表达与非小细胞肺癌（NSCLC）细胞的低分化和高pTNM分期密切相关。体外和体内分析表明，ZNF326显著促进细胞周期进程、集落形成、增殖和NSCLC移植瘤的生长。染色质免疫沉淀测序、双荧光素酶测定和电泳迁移转移试验证实，ZNF326的C2H2结构结合ERCC1启动子-833至-875 bp区域，启动转录活性。这种结合促进了CyclinB1的合成和细胞周期的进展。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。
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.