Hypomethylation of lncRNA H19 as a potential prognostic biomarker for oral squamous cell carcinoma

Eun Young Lee; Jae Min Song; Hye Jung Kim; Hae Ryoun Park

doi:10.1016/j.archoralbio.2021.105214

Hypomethylation of lncRNA H19 as a potential prognostic biomarker for oral squamous cell carcinoma

Arch Oral Biol. 2021 Sep:129:105214. doi: 10.1016/j.archoralbio.2021.105214. Epub 2021 Jul 22.

Authors

Eun Young Lee¹, Jae Min Song², Hye Jung Kim³, Hae Ryoun Park⁴

Affiliations

¹ Department of Oral Pathology, and BK21 PLUS Project, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea; Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea.
² Department of Oral and Maxillofacial Surgery, Pusan National University, Yangsan, 50612, Gyeongsangnam-do, Republic of Korea; Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, 50612, Gyeongsangnam-do, Republic of Korea.
³ Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea. Electronic address: kimhj2850@naver.com.
⁴ Department of Oral Pathology, and BK21 PLUS Project, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea; Periodontal Disease Signaling Network Research Center (MRC), School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea; Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, 50612, Gyeongsangnam-do, Republic of Korea. Electronic address: parkhr@pusan.ac.kr.

PMID: 34333230
DOI: 10.1016/j.archoralbio.2021.105214

Abstract

Objectives: Dysregulated DNA methylation is common in cancers and is considered one of the most important triggers in cancer development and progression. The expression and promoter methylation status of long non-coding RNA (lncRNA) H19 play a key role in several cancers, but its role is unclear in oral cancer. The aim of this study was to evaluate the potential of lncRNA H19 as a prognostic biomarker for oral cancer.

Designs: The transcript levels and the methylation status of lncRNA H19 in OSCC cell lines and OSCC patient tissues were investigated by quantitative real-time RT-PCR (qRT-PCR) and methylation-specific PCR (MSP). Methylation ratio (%) were calculated from the intensity of the MSP in the gel image and Kaplan-Meier survival analysis of OSCC patient survival was performed for patients grouped according to the lncRNA H19 promoter methylation ratio.

Results: lncRNA H19 was highly expressed and its promoter region was hypomethylated in OSSC cell lines as compared to normal control. Almost all OSCC patients tissues (63 out of 65, 97 %) showed hypomethylation of lncRNA H19 compared to normal oral mucosa tissues. There was a significant correlation between methylation ratio and tumor histopathologic grade. OSCC patients with hypomethylation of lncRNA H19 had a significantly lower 5-year survival rate.

Conclusions: Hypomethylation of lncRNA H19 may serve as a potential prognostic biomarker for oral cancer.

Keywords: Hypomethylation; Methylation-specific PCR; Oral squamous cell carcinoma; lncRNA H19.

MeSH terms

Biomarkers
Carcinoma, Squamous Cell* / genetics
DNA Methylation
Gene Expression Regulation, Neoplastic
Head and Neck Neoplasms*
Humans
Mouth Neoplasms* / genetics
Prognosis
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
Squamous Cell Carcinoma of Head and Neck

Substances

Biomarkers
H19 long non-coding RNA
RNA, Long Noncoding