Abstract
The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased rapidly in the United States, driven by rising human papillomavirus (HPV) infections in the U.S. population. HPV-positive OPSCC patients have a better prognosis than HPV-negative patients. To gain insights into the unique biology of HPV(+) OPSCC that may contribute to its clinical behaviors, we performed a multi-stage epigenome-wide methylation profiling of leukocyte and tumor DNA in OPSCC patients and compared the methylation levels of CpG sites between HPV(+) and HPV(−) OPSCC patients. We identified and validated a significantly differentially methylated region (DMR) of 1,355 bp encompassing non-coding RNA 886 (nc886) gene and its promoter region. Nc886 is hypermethylated in both leukocytes and tumor DNA of HPV(+) OPSCC patients. Homozygous knockout of nc886 by CRISPR-Cas9 in head and neck cell lines was lethal, but nc886 could be knocked out on the background of protein kinase R (PKR) knockout. Our data suggest that HPV induces nc886 hypermethylation, and nc886 acts as both a viral sensor and a tumor sensor in OPSCC patients and contribute to the better prognosis of HPV(+) OPSCC patients. Nc886 may become a therapeutic target in OPSCC.
Original language | English (US) |
---|---|
Pages (from-to) | 596-605 |
Number of pages | 10 |
Journal | Molecular Therapy - Nucleic Acids |
Volume | 30 |
DOIs | |
State | Published - Dec 13 2022 |
Keywords
- DNA methylation
- HPV
- MT: Non-coding RNAs
- OPSCC
- PKR
- leukocyte
- nc886
- non-coding RNA
- oropharyngeal cancer
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
MD Anderson CCSG core facilities
- Biostatistics Resource Group