Faculty, Staff and Student Publications

Publication Date

12-13-2022

Journal

Molecular Therapy Nucleic Acids

DOI

10.1016/j.omtn.2022.11.012

PMID

36514351

PMCID

PMC9722395

PubMedCentral® Posted Date

November 2022

PubMedCentral® Full Text Version

Post-print

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.

Keywords

MT: Non-coding RNAs, oropharyngeal cancer, OPSCC, HPV, DNA methylation, non-coding RNA, nc886, PKR, leukocyte

Published Open-Access

yes

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