N6-methyladenosine (m6A) modification is the most abundant RNA modification in eukaryotes and is widely involved in the regulation of RNA nuclear export, splicing, translation and degradation. Increasing evidence shows that m6A methylation modification of circular RNA (circRNA) has great potential in metabolism, immunity and benign and malignant diseases. Here, we review the research status of circRNA m6A methylation modification in physiological processes, malignant tumors and oral diseases. It has been shown that m6A methylation can regulate circRNA by regulating circRNA translation, promoting circRNA nuclear output, and promoting circRNA degradation; M6A-modified circRNA plays a regulatory role in immunity, the reproductive system, myogenesis and development, and malignant tumors; and the M6A methyltransferase METTL3 promotes the occurrence of oral squamous cell carcinoma (OSCC) through m6A modification mediated by YTHDF1. The high expression of METTL14 can effectively reduce the proliferation, migration and invasion of OSCC. There is little research on circRNA m6A methylation modification in the oral cavity, which is limited to preliminary research in ameloblastoma and oral implant bone absorption. It has broad research prospects in the treatment of major oral diseases (such as potential oral malignant diseases and OSCC).
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Open Access
Review Article
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Open Access
Basic Study
Issue
To find any differentially expressed circRNAs in oral leukoplakia (OLK) and oral lichen planus (OLP), to investigate the possible role of circRNAs in the pathogenesis of these two diseases.
This study obtained hospital ethical approval. High-throughput sequencing was used to detect differentially expressed circRNAs in OLK, OLP, oral squamous cell carcinoma and normal oral mucosal tissues. CircRNAs were verified by qRT-PCR, enzyme tolerance assays and Sanger sequencing. GO functional analysis and KEGG pathway analysis were performed to predict the functions of circRNAs in OLP. TargetScan and miRanda were applied to predict targeted miRNAs and mRNAs of circRNAs, and ceRNA networks were mapped.
A total of 49 circRNAs were differentially expressed in OLK and OLP together, including 30 upregulated and 19 downregulated circRNAs. The five circRNAs confirmed with RT-qPCR, including circHLA-C, circRNF13, circTTN, circSEPN2 and circALDH3A2, were all abnormally expressed in OLK and OLP, among which circHLA-C was a key circRNA with trans splice sites, which was validated by expanding the sample size. ROC curve analysis showed that the area under the circHLA-C curve for predicting OLK was 0.955, and the area under the circHLA-C curve for predicting OLP was 0.988. GO functional analysis showed enrichment of many biological processes related to the immune process. The KEGG pathway with the highest enrichment score was"Natural killer cell mediated cytotoxicity". HLA-C was significantly enriched in these processes/pathways. CeRNA network analysis showed that circHLA-C interacted with a variety of miRNAs, such as hsa-miR-26a-5p, hsa-miR-129-5p, and hsa-miR-29a-3p.
Many circRNAs were differentially expressed in both OLK and OLP, circHLA-C being the most elevated. CircHLA-C is valuable for the early diagnosis of OLK and OLP and may serve as a potential biomarker for the diagnosis and prognosis of OLK and OLP.
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