METTL14-upregulated miR-6858 triggers cell apoptosis in keratinocytes of oral lichen planus through decreasing GSDMC

Autor: Xiangyu Wang, Shuangting Li, Huimin Song, Yan Ding, Ruifang Gao, Xiaotong Shi, Ran Li, Xuejun Ge
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Communications Biology, Vol 6, Iss 1, Pp 1-11 (2023)
Druh dokumentu: article
ISSN: 2399-3642
DOI: 10.1038/s42003-023-05360-6
Popis: Abstract Oral lichen planus (OLP), a chronic inflammatory disorder, is characterized by the massive cell apoptosis in the keratinocytes of oral mucosa. However, the mechanism responsible for triggering oral keratinocyte apoptosis is not fully explained. Here, we identify that Gasdermin C (GSDMC) downregulation contributes to apoptosis in human oral keratinocytes. Mechanistically, we describe that activated nuclear factor kappa B (NF-κB) pathway induces overexpression of methyltransferase-like 14 (METTL14), which increases N 6-adenosine methylation (m6A) levels in the epithelial layer of OLP. m6A modification is capable of regulating primary miR-6858 processing and alternative splicing, leading to miR-6858 increases. miR-6858 can bind and promote GSDMC mRNA degradation. Forced expression of GSDMC is able to rescue cell apoptosis in human oral keratinocyte models resembling OLP. Collectively, our data unveil that m6A modification regulates miR-6858 production to decrease GSDMC expression and to trigger keratinocyte apoptosis in the context of OLP.
Databáze: Directory of Open Access Journals
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