ELF1 expression in prostate cells reduces oncogenic ETS functions and promotes senescence and sensitivity to chemotherapy through distinct gene expression programs [ChIP-seq]

Aberrant overexpression of oncogenic ETS factors through chromosomal rearrangments is the most common genomic event in primary prostate tumor and these factors have been well studied. Loss of ELF1, another ETS transcription factor family member, is a common event in prostate cancer, but the function of ELF1 has not been described within the prostate. Studies of ELF1 in different tissue types has determined that it can be important for oncogeneis or tumor suppression. Here, we show that ELF1 is a novel prostate tumor suppressor by hindering oncogenic ETS function at cell migration related genes, but also that ELF1 has the ability to regulate senescence and chemotherapy resistance. Next generation sequencing was used to determine gene expression changes in RWPE-1 cells upon addition of an oncogenic ETS factor and then with the loss of ELF1 through an shRNA knockdown. Genomic binding locations were also determined for ELF1 and ERG, through ChIP-seq to identify any cobound or unique regions. The combination of this data indicates that ELF1 repressed migration related genes which ERG activates, but ELF1 also uniquely binds genes related to cell senescence and activates their transcription. There, these data indicate a novel tumor suppressive mechanism for ELF1 within the prostate and better characterizes its function within this cell type.

通过染色体重排导致致癌性ETS转录因子家族（ETS transcription factor family）的异常过表达，是原发性前列腺肿瘤中最常见的基因组事件，且此类因子已得到充分研究。ELF1（E74-like factor 1）作为另一类ETS转录因子家族成员，其缺失是前列腺癌中的常见事件，但ELF1在前列腺组织中的功能尚未被阐明。针对不同组织类型中ELF1的研究表明，其既可在肿瘤发生中发挥重要作用，也可作为肿瘤抑制因子。本研究证实，ELF1是一种新型前列腺肿瘤抑制因子：它既可通过靶向细胞迁移相关基因抑制致癌性ETS因子的功能，同时还能够调控细胞衰老与化疗耐药性。本研究通过下一代测序（Next Generation Sequencing）技术，检测了RWPE-1细胞在过表达致癌性ETS因子，以及通过短发夹RNA（short hairpin RNA，shRNA）敲低ELF1后的基因表达变化情况。研究还通过染色质免疫沉淀测序（Chromatin Immunoprecipitation sequencing，ChIP-seq）技术，确定了ELF1与ERG（ETS-related gene）的基因组结合位点，以识别二者的共结合区域或独有结合区域。综合分析上述数据可知，ELF1可抑制ERG所激活的细胞迁移相关基因；同时ELF1还可特异性结合与细胞衰老相关的基因并激活其转录。综上，本研究数据揭示了ELF1在前列腺内的新型肿瘤抑制机制，并进一步阐明了其在该细胞类型中的功能。

搜集汇总

背景与挑战

背景概述

该数据集是一个人类前列腺细胞的ChIP-seq研究，发布于2022年，旨在探究转录因子ELF1在前列腺中的肿瘤抑制机制。研究发现ELF1通过抑制致癌ETS因子（如ERG）在迁移相关基因上的功能，同时独特地结合并激活衰老相关基因，从而促进细胞衰老和化疗敏感性，揭示了ELF1在前列腺癌中的新型抑癌作用。数据集包含3个样本，总大小4.73 GB，涉及PC3和RWPE-1细胞系。