Integrative analysis based on ATAC-seq and RNA-seq reveals a novel oncogene PRPF3 in hepatocellular carcinoma
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 util...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-11-01
|
| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13148-024-01769-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850061909083029504 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Yi Bai |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-c5dba5daadcc4fba9fb1d995ac991f3c |
| institution | DOAJ |
| issn | 1868-7083 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj-art-c5dba5daadcc4fba9fb1d995ac991f3c2025-08-20T02:50:04ZengBMCClinical Epigenetics1868-70832024-11-0116111810.1186/s13148-024-01769-wIntegrative analysis based on ATAC-seq and RNA-seq reveals a novel oncogene PRPF3 in hepatocellular carcinomaYi Bai0Xiyue Deng1Dapeng Chen2Shuangqing Han3Zijie Lin4Zhongmin Li5Wen Tong6Jinming Li7Tianze Wang8Xiangyu Liu9Zirong Liu10Zilin Cui11Yamin Zhang12Department of Hepatobiliary Surgery, School of Medicine, Tianjin First Central Hospital, Nankai UniversityTianjin First Central Hospital Clinic Institute, Tianjin Medical UniversityTianjin First Central Hospital Clinic Institute, Tianjin Medical UniversityTianjin First Central Hospital Clinic Institute, Tianjin Medical UniversityTianjin First Central Hospital Clinic Institute, Tianjin Medical UniversityDepartment of Hepatobiliary and Pancreatic Surgery, Tianjin Nankai HospitalTianjin First Central Hospital Clinic Institute, Tianjin Medical UniversityTianjin First Central Hospital Clinic Institute, Tianjin Medical UniversitySchool of Medicine, Nankai UniversitySchool of Medicine, Nankai UniversityDepartment of Hepatobiliary Surgery, School of Medicine, Tianjin First Central Hospital, Nankai UniversityDepartment of Hepatobiliary Surgery, School of Medicine, Tianjin First Central Hospital, Nankai UniversityDepartment of Hepatobiliary Surgery, School of Medicine, Tianjin First Central Hospital, Nankai UniversityAbstract 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.https://doi.org/10.1186/s13148-024-01769-wHepatocellular carcinomaAssay of transposase accessible chromatin sequencingPRPF3Transcription factorEpigenetics |
| spellingShingle | 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 Integrative analysis based on ATAC-seq and RNA-seq reveals a novel oncogene PRPF3 in hepatocellular carcinoma Clinical Epigenetics Hepatocellular carcinoma Assay of transposase accessible chromatin sequencing PRPF3 Transcription factor Epigenetics |
| title | Integrative analysis based on ATAC-seq and RNA-seq reveals a novel oncogene PRPF3 in hepatocellular carcinoma |
| title_full | Integrative analysis based on ATAC-seq and RNA-seq reveals a novel oncogene PRPF3 in hepatocellular carcinoma |
| title_fullStr | Integrative analysis based on ATAC-seq and RNA-seq reveals a novel oncogene PRPF3 in hepatocellular carcinoma |
| title_full_unstemmed | Integrative analysis based on ATAC-seq and RNA-seq reveals a novel oncogene PRPF3 in hepatocellular carcinoma |
| title_short | Integrative analysis based on ATAC-seq and RNA-seq reveals a novel oncogene PRPF3 in hepatocellular carcinoma |
| title_sort | integrative analysis based on atac seq and rna seq reveals a novel oncogene prpf3 in hepatocellular carcinoma |
| topic | Hepatocellular carcinoma Assay of transposase accessible chromatin sequencing PRPF3 Transcription factor Epigenetics |
| url | https://doi.org/10.1186/s13148-024-01769-w |
| work_keys_str_mv | AT yibai integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma AT xiyuedeng integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma AT dapengchen integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma AT shuangqinghan integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma AT zijielin integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma AT zhongminli integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma AT wentong integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma AT jinmingli integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma AT tianzewang integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma AT xiangyuliu integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma AT zirongliu integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma AT zilincui integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma AT yaminzhang integrativeanalysisbasedonatacseqandrnaseqrevealsanoveloncogeneprpf3inhepatocellularcarcinoma |