CircHLA-C: A significantly upregulated circRNA co-existing in oral leukoplakia and oral lichen planus

Jingwen Yang; Yuhan Song; Siming Xu; Shuyun Ge; Zhou Haiwen

doi:10.1080/15476278.2023.2234504

CircHLA-C: A significantly upregulated circRNA co-existing in oral leukoplakia and oral lichen planus

Organogenesis. 2023 Dec 31;19(1):2234504. doi: 10.1080/15476278.2023.2234504.

Authors

Jingwen Yang^{1

2

3

4}, Yuhan Song^{1

2

3

4}, Siming Xu^{1

2

3

4}, Shuyun Ge^{1

2

3

4}, Zhou Haiwen^{1

2

3

4}

Affiliations

¹ Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² College of Stomatology, Shanghai Jiao Tong UniversityNational Center for Stomatology, Shanghai, China.
³ National Clinical Research Center for Oral Diseases, Shanghai, China.
⁴ Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.

Abstract

Background: Oral leukoplakia (OLK) and oral lichen planus (OLP) are common precancerous lesions of the oral mucosa. The role of circular RNAs (circRNAs) in OLK and OLP is unclear. The aim of this study was to evaluate the circRNA expression profiles of OLK and OLP, and further explore the potential role of circRNAs in the pathogenesis of these two diseases.

Methods: High throughput sequencing technology was performed to detect the differentially expressed circRNA in OLK (n = 6), OLP (n = 6), oral squamous cell carcinoma (n = 6), and normal oral mucosa tissues (n = 6). Expression of selected circRNAs was validated by qRT-PCR, enzyme tolerance assay, and Sanger sequencing. Expanded sample size validation was done in 20 tissue pairs. The biological processes and signal pathways involved in differential circRNA were analyzed by GO and KEGG enrichment. TargetScan and MiRanda were used to predict miRNAs downstream of circRNA and draw competitive endogenous RNA network diagram.

Results: Forty-nine circRNAs were significantly altered in OLK and OLP, including 30 upregulated and 19 downregulated circRNAs. The five selected circRNAs were validated by qRT-PCR, Sanger sequencing, and RNase R assay. GO and KEGG analyses indicated that the upregulated circHLA-C may be involved in the biological process of immune function of OLK and OLP. Bioinformatics analysis indicated that circHLA-C may be involved in the progression of OLK and OLP as a ceRNA. In validation with expanded sample size, PCR results showed that circHLA-C expression was significantly upregulated in OLK and OLP. ROC analysis indicated that circHLA-C has potential diagnostic value with good accuracy and specificity.

Conclusion: Our study revealed that circHLA-C is the most significantly upregulated circRNA co-existing in OLK and OLP, and we preliminarily discuss the role of circHLA-C in the etiopathogenesis and progression of OLK and OLP.

Keywords: Biomarkers; CircHLA-C; Oral leukoplakia (OLK); Oral lichen planus (OLP); circRNA; high-throughput sequencing; malignant transformation; oral potentially malignant disorders.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Squamous Cell* / pathology
Humans
Leukoplakia, Oral / genetics
Leukoplakia, Oral / pathology
Lichen Planus, Oral* / genetics
Lichen Planus, Oral* / pathology
MicroRNAs*
Mouth Neoplasms* / genetics
Mouth Neoplasms* / pathology
RNA, Circular / genetics
RNA, Circular / metabolism

Substances

RNA, Circular
MicroRNAs

Grants and funding

This study was supported by the grants from The National Natural Science Foundation of China (No. 81170968). Construction and management of biological sample bank for potential malignant diseases of oral mucosal(YBKA201912).