Integrative analysis based on ATAC-seq and RNA-seq reveals a novel oncogene PRPF3 in hepatocellular carcinoma.

IF 4.8 2区 医学 Q1 GENETICS & HEREDITY
Yi Bai, Xiyue Deng, Dapeng Chen, Shuangqing Han, Zijie Lin, Zhongmin Li, Wen Tong, Jinming Li, Tianze Wang, Xiangyu Liu, Zirong Liu, Zilin Cui, Yamin Zhang
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Abstract

Background: Assay of Transposase Accessible Chromatin Sequencing (ATAC-seq) is a high-throughput sequencing technique that detects open chromatin regions across the genome. These regions are critical in facilitating transcription factor binding and subsequent gene expression. Herein, we utilized ATAC-seq to identify key molecular targets regulating the development and progression of hepatocellular carcinoma (HCC) and elucidate the underlying mechanisms.

Methods: We first compared chromatin accessibility profiles between HCC and normal tissues. Subsequently, RNA-seq data was employed to identify differentially expressed genes (DEGs). Integrating ATAC-seq and RNA-seq data allowed the identification of transcription factors and their putative target genes associated with differentially accessible regions (DARs). Finally, functional experiments were conducted to investigate the effects of the identified regulatory factors and corresponding targets on HCC cell proliferation and migration.

Results: Enrichment analysis of DARs between HCC and adjacent normal tissues revealed distinct signaling pathways and regulatory factors. Upregulated DARs in HCC were enriched in genes related to the MAPK and FoxO signaling pathways and associated with transcription factor families like ETS and AP-1. Conversely, downregulated DARs were associated with the TGF-β, cAMP, and p53 signaling pathways and the CTCF family. Integration of the datasets revealed a positive correlation between specific DARs and DEGs. Notably, PRPF3 emerged as a gene associated with DARs in HCC, and functional assays demonstrated its ability to promote HCC cell proliferation and migration. To the best of our knowledge, this is the first report highlighting the oncogenic role of PRPF3 in HCC. Furthermore, ZNF93 expression positively correlated with PRPF3, and ChIP-seq data indicated its potential role as a transcription factor regulating PRPF3 by binding to its promoter region.

Conclusion: This study provides a comprehensive analysis of the epigenetic landscape in HCC, encompassing both chromatin accessibility and the transcriptome. Our findings reveal that ZNF93 promotes the proliferation and motility of HCC cells through transcriptional regulation of a novel oncogene, PRPF3.

基于 ATAC-seq 和 RNA-seq 的整合分析揭示了肝细胞癌中的新型癌基因 PRPF3。
背景:转座酶可进入染色质测序(ATAC-seq)是一种高通量测序技术,可检测整个基因组的开放染色质区域。这些区域对促进转录因子结合和随后的基因表达至关重要。在此,我们利用 ATAC-seq 鉴定调控肝细胞癌(HCC)发生和发展的关键分子靶点,并阐明其潜在机制:我们首先比较了HCC和正常组织的染色质可及性图谱。方法:我们首先比较了HCC和正常组织的染色质可及性图谱,然后利用RNA-seq数据鉴定差异表达基因(DEGs)。整合ATAC-seq和RNA-seq数据后,我们确定了与差异可及区域(DARs)相关的转录因子及其假定靶基因。最后,研究人员进行了功能实验,以研究已确定的调控因子和相应靶标对 HCC 细胞增殖和迁移的影响:结果:HCC与邻近正常组织之间的DARs富集分析揭示了不同的信号通路和调控因子。HCC中上调的DARs富集在与MAPK和FoxO信号通路相关的基因中,并与ETS和AP-1等转录因子家族相关。相反,下调的 DAR 与 TGF-β、cAMP 和 p53 信号通路以及 CTCF 家族有关。整合数据集后发现,特定 DAR 与 DEGs 之间存在正相关。值得注意的是,PRPF3成为了与HCC中DARs相关的基因,功能测试证明了它促进HCC细胞增殖和迁移的能力。据我们所知,这是第一份强调 PRPF3 在 HCC 中致癌作用的报告。此外,ZNF93的表达与PRPF3呈正相关,ChIP-seq数据表明ZNF93通过与PRPF3的启动子区域结合,可能起到转录因子调控PRPF3的作用:本研究全面分析了 HCC 的表观遗传景观,包括染色质可及性和转录组。我们的研究结果表明,ZNF93通过转录调控新型癌基因PRPF3,促进了HCC细胞的增殖和运动。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
自引率
5.30%
发文量
150
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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