Department of Oral Mucosal Diseases, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
College of Stomatology, Shanghai Jiao Tong UniversityNational Center for Stomatology, Shanghai, China.
Organogenesis. 2023 Dec 31;19(1):2234504. doi: 10.1080/15476278.2023.2234504.
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.
High throughput sequencing technology was performed to detect the differentially expressed circRNA in OLK ( = 6), OLP ( = 6), oral squamous cell carcinoma ( = 6), and normal oral mucosa tissues ( = 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.
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.
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.
口腔白斑病（OLK）和口腔扁平苔藓（OLP）是常见的口腔黏膜癌前病变。环状 RNA（circRNA）在 OLK 和 OLP 中的作用尚不清楚。本研究旨在评估 OLK 和 OLP 的 circRNA 表达谱，并进一步探讨 circRNA 在这两种疾病发病机制中的潜在作用。
采用高通量测序技术检测 6 例 OLK、6 例 OLP、6 例口腔鳞状细胞癌和 6 例正常口腔黏膜组织中的差异表达 circRNA。采用 qRT-PCR、酶耐受试验和 Sanger 测序验证选定 circRNA 的表达。在 20 对组织中进行了扩大样本量验证。通过 GO 和 KEGG 富集分析，分析差异 circRNA 涉及的生物学过程和信号通路。利用 TargetScan 和 MiRanda 预测 circRNA 下游的 miRNA，并绘制竞争性内源性 RNA 网络图。
在 OLK 和 OLP 中发现 49 个 circRNA 显著改变，包括 30 个上调和 19 个下调 circRNA。通过 qRT-PCR、Sanger 测序和 RNase R 试验验证了 5 个选定的 circRNA。GO 和 KEGG 分析表明，上调的 circHLA-C 可能参与 OLK 和 OLP 的免疫功能的生物学过程。生物信息学分析表明，circHLA-C 可能作为 ceRNA 参与 OLK 和 OLP 的进展。在扩大样本量验证中，PCR 结果显示 circHLA-C 在 OLK 和 OLP 中表达显著上调。ROC 分析表明，circHLA-C 具有良好的准确性和特异性，具有潜在的诊断价值。
本研究表明，circHLA-C 是 OLK 和 OLP 中最显著上调的共表达 circRNA，我们初步探讨了 circHLA-C 在 OLK 和 OLP 发病机制和进展中的作用。
