Integrative Multi-Omics Analysis Identifies a Functional Enhancer Driving Tumorigenesis in Head and Neck Squamous Cell Carcinoma
Year: 2026
Type: preprint
Abstract: Enhancer is a critical epigenetic feature in head and neck squamous cell carcinoma (HNSCC), yet the functional roles of individual enhancers remain poorly understood. Here, we conducted an integrative multi-omics analysis based on publicly available ATAC-seq, H3K27ac ChIP-seq, transcriptomic profiling, and genetic association datasets to systematically map HNSCC-associated enhancers and their target genes. Integrating ATAC-seq and H3K27ac ChIP-seq, we identified 20,362 enhancers and 18,040 enhancer-associated genes, highlighting widespread regulatory complexity. Functional characterization of the TERT -associated enhancer GH05J001312 (GRCh38/hg38: chr5:1312099-1317743) revealed strong transcriptional activity in HNSCC. CRISPR-mediated deletion of a core sequence significantly reduced TERT expression, impaired cellular proliferation in vitro , and suppressed tumor growth in vivo , confirming its role as a key cis-regulatory element. RNA-seq analysis of enhancer-edited cells uncovered 742 differentially expressed genes enriched in cancer-related pathways, including MAPK and IL-17 signaling, indicating a broad transcriptional impact. Collectively, our findings establish GH05J001312 as a functional enhancer driving oncogenic programs in HNSCC and suggest enhancer-targeted strategies as a potential therapeutic avenue.
Authors: Pengfei Xu, Xiaorong Liu, Jane Jingya Pu, Xiaoling Lu, Victor Lee, Evelyn Yilin Wang, Qianhui Jiang, Dan Yu, Bin Yan, Jinlin Song, Qi Zhong, Ping Yang, Nhan L. Tran, Xinyuan Guan, Yu-Xiong Su, Junwen Wang
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7127984480