Long non-coding RNA ZFY-AS1 represses periodontitis tissue inflammation and oxidative damage via modulating microRNA-129-5p/DEAD-Box helicase 3 X-linked axis

Abstract

A large number of studies have manifested long non-coding RNA (lncRNA) is involved in the modulation of the development of periodontitis, but the specific mechanism has not been fully elucidated. The purpose of this study was to explore the biological function and latent molecular mechanism of lncZFY-AS1 in periodontitis. The results clarified lncZFY-AS1 and DEAD-Box Helicase 3 X-Linked (DDX3X) were up-regulated, but microRNA (miR)-129-5p was down-regulated in periodontitis. Knockdown of lncZFY-AS2 or overexpression of miR-129-5p decreased macrophage infiltration and periodontal membrane cell apoptosis, increased cell viability, repressed inflammatory factors and nuclear factor kappa B activation, reduced oxidative stress, but promoted nuclear factor-E2-related factor 2/heme oxygenase 1 expression. LncZFY-AS1 elevation further aggravated periodontitis inflammation, oxidative stress, and apoptosis. LncZFY competitively adsorbed miR-129-5p to mediate DDX3X expression. Knockdown lncZFY’s improvement effect on periodontitis was reversed by depressive miR-129-5p or enhancive DDX3X. In conclusion, these data suggest lncZFY-AS1 promotes inflammatory injury and oxidative stress in periodontitis by competitively binding to miR-129-5p and mediating DDX3X expression. LncZFY-AS1/miR-129-5p/DDX3X may serve as a novel molecular target for treatment of periodontitis in the future.

Exosomal miR‐205‐5p derived from periodontal ligament stem cells attenuates the inflammation of chronic periodontitis via targeting XBP1

“…40 MiR-129-5p is also downregulated in periodontitis, which plays a regulatory role in inhibiting macrophage infiltration, apoptosis, inflammation, and oxidative stress. 41 In this research, miR-205-5p was downregulated in LPStreated PDLSCs, indicating a therapeutic potential for CP. Exosomes play a key role in substance exchange and signal communication among cells, presenting diagnostic and therapeutic potential for human diseases.…”

“… 40 MiR‐129‐5p is also downregulated in periodontitis, which plays a regulatory role in inhibiting macrophage infiltration, apoptosis, inflammation, and oxidative stress. 41 In this research, miR‐205‐5p was downregulated in LPS‐treated PDLSCs, indicating a therapeutic potential for CP.…”

Revealing a potential necroptosis‐related axis (RP11‐138A9.1/hsa‐miR‐98‐5p/ZBP1) in periodontitis by construction of the ceRNA network

“…Moreover, lncRNAs have lately been reported to be associated with the regulation of gene expression in periodontitis by lncRNA-miRNA-mRNA regulatory axes. [42][43][44] Until now, the molecular signatures of necroptosis-related lncRNAs in periodontitis have not been elucidated. Thus, this study is aimed at identifying the necroptosis-related lncRNA-miRNA-mRNA regulatory axes and exploring the underlying mechanisms to further comprehend the pathogenesis of periodontitis.…”

“…Necroptosis, as an independent process of apoptosis and pyroptosis, 39 a newly discovered cell death mode that is highly proinflammatory, was recently found to be involved in periodontitis, 40,41 which raises the possibility that the necroptosis pathway could be a new pharmacological target in periodontitis. Moreover, lncRNAs have lately been reported to be associated with the regulation of gene expression in periodontitis by lncRNA–miRNA–mRNA regulatory axes 42–44 . Until now, the molecular signatures of necroptosis‐related lncRNAs in periodontitis have not been elucidated.…”

“…To reduce the differences in the combination of batches of samples, we used the ComBat method in R package "SVA" to conduct batch correction of the combined data. Then, from previous literature [39][40][41][42][43][44][45][46][47] and necroptosis gene set (M24779.gmt) from the Gene Set Enrichment Analysis (GSEA) (http://www.gsea-msigdb.org/gsea/index.jsp), a total of 21 necroptosis-related genes (NSGs) (ALDH2, CXCL1, EZH2, FADD, FAS, FASLG, HMGB1, MLKL, NDRG2, NR2C2, PGAM5, RIPK1, RIPK3, TLR2, TLR3, TLR4, TNF, TNFRSF1A, TRAF2, USP22, and ZBP1) were obtained.…”