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Integrative Analysis of Multi-omics Data Reveals AP-1 Is a Key Regulator in Intrahepatic Cholangiocarcinoma

24 Pages Posted: 15 May 2020

See all articles by Ke He

Ke He

Department of General Surgery, Guangdong Second Provincial General Hospital

Yuliang Feng

Department of General Surgery, Guangdong Second Provincial General Hospital

Sanqi An

Department of General Surgery, Guangdong Second Provincial General Hospital

Jianguo Xu

Department of General Surgery, Heyuan People's Hospital

Fei Liu

Department of General Surgery, Guangdong Second Provincial General Hospital

Qianshan Ding

Department of Gastroenterology, Renmin Hospital of Wuhan University

Wenxing Li

Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences

Zhenglin Xia

Department of General Surgery, Guangdong Second Provincial General Hospital

Guoan Xiang

Guangdong Second Provincial General Hospital - Department of General Surgery

More...

Abstract

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor with poor prognosis. Currently, its mechanism of pathogenesis remains elusive. In this study, we employed integrative -omics approaches (RNA-seq, ChIP-seq, and MNase-seq) to interrogate the epigenome in ICC. The results of ChIP-seq, differential gene expression, and MNase-seq analyses suggested that ICC cell lines exhibit less histone modification of cancer-related genes compared with a normal cell line. The region of different histone modification patterns is enrichment in sites of AP-1 motif. Subsequent analysis showed that ICC had different nucleosome occupancy in differentially expressed genes compared to a normal cell line. Furthermore, we found that AP-1 plays a key role in ICC and regulates ICC-related genes through its AP-1 binding site. This study is the first report showing the global features of histone modification, transcript, and nucleosome profiles in ICC; we also show that the transcription factor AP-1 might be a key target gene in ICC.

Funding Statement: This work was supported by granted from the National Natural Science Foundation of China (No. 81071990, No. 81641110); Science and Technology Program of Guangzhou, China (No. 201707010305); Youth Science Foundation of Guangdong Second Provincial General Hospital (No. YQ2016-001).

Declaration of Interests: The authors declare that they have no conflicts of interest.

Keywords: Intrahepatic cholangiocarcinoma, Histone modification, Nucleosome positioning, Data analysis, AP-1

Suggested Citation

He, Ke and Feng, Yuliang and An, Sanqi and Xu, Jianguo and Liu, Fei and Ding, Qianshan and Li, Wenxing and Xia, Zhenglin and Xiang, Guoan, Integrative Analysis of Multi-omics Data Reveals AP-1 Is a Key Regulator in Intrahepatic Cholangiocarcinoma (3/19/2020). Available at SSRN: https://ssrn.com/abstract=3559522 or http://dx.doi.org/10.2139/ssrn.3559522

Ke He (Contact Author)

Department of General Surgery, Guangdong Second Provincial General Hospital

Guangzhou, Guangdong
China

Yuliang Feng

Department of General Surgery, Guangdong Second Provincial General Hospital

Guangzhou, Guangdong
China

Sanqi An

Department of General Surgery, Guangdong Second Provincial General Hospital

Guangzhou, Guangdong
China

Jianguo Xu

Department of General Surgery, Heyuan People's Hospital

Heyuan
China

Fei Liu

Department of General Surgery, Guangdong Second Provincial General Hospital

Guangzhou, Guangdong
China

Qianshan Ding

Department of Gastroenterology, Renmin Hospital of Wuhan University

Wuhan
China

Wenxing Li

Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences

52 Sanlihe Rd.
Datun Road, Anwai
Beijing, Xicheng District 100864
China

Zhenglin Xia

Department of General Surgery, Guangdong Second Provincial General Hospital

Guangzhou, Guangdong
China

Guoan Xiang

Guangdong Second Provincial General Hospital - Department of General Surgery ( email )

Guangzhou
China

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