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小细胞肺癌中转录因子E2F1调控的靶基因

李尊岭, 焦飞, 马颖, 岳真, 孔丽君^*

滨州医学院生物化学与分子生物学教研室，烟台 264003

摘要

本研究组前期研究结果表明，转录因子E2F1在大约95%的小细胞肺癌组织中表达上调，而且与其浸润、转移密切相关，但是E2F1在小细胞肺癌中调控的靶基因未见报道。本研究旨在探索E2F1在小细胞肺癌细胞株H1688中调控的靶基因。染色体免疫共沉淀联合测序(chromatin immunoprecipitation sequencing, ChIP-seq)结果显示，在小细胞肺癌H1688细胞中，E2F1能够调控5 326个靶基因的表达，其中4 700个是结构基因，626个基因编码长链非编码RNA。基因功能注释(gene ontology, GO)和基因富集图谱(enrichment map)分析显示，E2F1调控的靶基因功能主要集中在3个方面：细胞周期调控、染色体和组蛋白修饰以及蛋白转运。MEME4.7.0软件分析显示，E2F1通过结合6个序列调控相关靶基因和长链非编码序列的表达。以上结果阐明了E2F1在小细胞肺癌中调控的靶基因，为进一步研究E2F1在小细胞肺癌发生、发展、浸润与转移、复发和耐药中的作用提供了实验依据。

关键词： E2F1; 小细胞肺癌; 染色体免疫共沉淀联合测序

Target genes regulated by transcription factor E2F1 in small cell lung cancer

LI Zun-Ling, JIAO Fei, MA Ying, YUE Zhen, KONG Li-Ju^*

Department of Biochemistry and Molecular Biology, Binzhou Medical University, Yantai 264003, China

Abstract

Previously, we have reported that transcription factor E2F1 expression is up-regulated in approximately 95% of small cell lung cancer tissue samples and closely associated with invasion and metastasis, but few studies have investigated specific target genes
regulated by E2F1 in this disease. The aim of this study was to clarify the target genes controlled by E2F1 in the small cell lung cancer cell line H1688. The results of chromatin immunoprecipitation sequencing (ChIP-seq) showed that total 5 326 potential target genes were identified, in which 4 700 were structural genes and 626 long non-coding RNAs (lncRNAs). Gene Ontology (GO) and enrichment map analysis results indicated that these target genes were associated with three main functions: (1) cell cycle regulation, (2) chromatin and histone modification, and (3) protein transport. MEME4.7.0 software was used to identify the E2F1 binding DNA motif, and six motifs were discovered for coding genes and lncRNAs. These results clarify the target genes of E2F1, and provide the experimental basis for further exploring the roles of E2F1 in tumorigenesis, development, invasion and metastasis, recurrence, and drug resistance in small cell lung cancer.

Key words: E2F1; small cell lung cancer; chromatin immunoprecipitation sequencing

收稿日期：　　录用日期：

通讯作者：孔丽君　　E-mail: yt_klijun@163.com

引用本文：

李尊岭, 焦飞, 马颖, 岳真, 孔丽君. 小细胞肺癌中转录因子E2F1调控的靶基因[J]. 生理学报 2016; 68 (3): 276-284.

LI Zun-Ling, JIAO Fei, MA Ying, YUE Zhen, KONG Li-Ju. Target genes regulated by transcription factor E2F1 in small cell lung cancer. Acta Physiol Sin 2016; 68 (3): 276-284 (in Chinese with English abstract).