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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,Ch IP-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。
Our previous study showed that E2F1 is upregulated in about 95% of small cell lung cancer tissues and closely related to its infiltration and metastasis. However, no target gene for E2F1 regulated in small cell lung cancer has been reported. This study aimed to explore the target genes regulated by E2F1 in small cell lung cancer cell line H1688. ChIP-seq showed that E2F1 regulates 5 326 target genes in small cell lung cancer H1688 cells, of which 4 700 are structural genes and 626 genes encode Long chain non-coding RNA. Gene ontology (GO) and enrichment map analysis showed that the function of E2F1-regulated target genes mainly concentrated on three aspects: cell cycle regulation, chromosome and histone modification, and protein transport. MEME4.7.0 software analysis showed that E2F1 regulates the expression of related target genes and long-chain non-coding sequences by binding to 6 sequences. The above results elucidated the target genes regulated by E2F1 in small cell lung cancer and provided experimental evidence for further study on the role of E2F1 in the occurrence and development of small cell lung cancer, invasion and metastasis, recurrence and drug resistance.