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

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.