期刊
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
卷 11, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcimb.2021.785169
关键词
cervical cancer; HPV integration; Hi-C; TAD boundary; gene expression
资金
- National Natural Science Foundation of China [81771529]
- Special Fund Project of Fundamental Research Funds for the Central Universities of Tongji University [22120190214]
- Shanghai Science and Technology Development Foundation [21S31905100]
- East Hospital initial foundation [DFRC201917]
- Shanghai Municipal Health Commission [20194Y0156]
This study investigated the impact of HPV16 integration on chromosome structure and gene expression in cervical cells. The results showed significant genomic variation and differential gene expression in the integrated chromosome, affecting topologically associated domain boundaries and tumor suppressor gene expression. This research provides valuable insights into the structural changes induced by HPV16 integration and its role in tumorigenesis, contributing to the understanding of the cervical carcinogenic mechanism.
High-risk human papillomavirus (hrHPV) infection and integration were considered as essential onset factors for the development of cervical cancer. However, the mechanism on how hrHPV integration influences the host genome structure remains not fully understood. In this study, we performed in situ high-throughput chromosome conformation capture (Hi-C) sequencing, chromatin immunoprecipitation and sequencing (ChIP-seq), and RNA-sequencing (RNA-seq) in two cervical cells, 1) NHEK normal human epidermal keratinocyte; and 2) HPV16-integrated SiHa tumorigenic cervical cancer cells. Our results reveal that the HPV-LINC00393 integrated chromosome 13 exhibited significant genomic variation and differential gene expression, which was verified by calibrated CTCF and H3K27ac ChIP-Seq chromatin restructuring. Importantly, HPV16 integration led to differential responses in topologically associated domain (TAD) boundaries, with a decrease in the tumor suppressor KLF12 expression downstream of LINC00393. Overall, this study provides significant insight into the understanding of HPV16 integration induced 3D structural changes and their contributions on tumorigenesis, which supplements the theory basis for the cervical carcinogenic mechanism of HPV16 integration.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据