ABSTRACT
@#Congenital cleft lip and/or palate (CL/P) is a common malformation of maxillofacial development. At present, it is believed that the etiology of congenital cleft lip and palate mainly results from genetic factors and environmental factors. Epigenetic changes induced by environmental factors may be the key factor in the occurrence of fetal congenital malformations. As one of the important epigenetic modifications, DNA methylation has been widely and deeply studied in many fields, but as a link between the individual and the environment, its application in CL/P is limited. Existing studies have shown that DNA methylation is closely related to the occurrence of cleft lip and palate. Stimulation of folate deficiency, smoking, pollutant exposure and other environmental factors can induce changes in the state of DNA methylation, thus affecting gene expression in the development of lip and palate and leading to the occurrence of deformities.
ABSTRACT
BACKGROUND: Non-syndromic cleft lip and/or palate (NSCL/P) is a common maxillofacial birth defect, and the etiology of which is complex and still unclear. Accumulating studies indicate that long non-coding RNAs(lncRNAs) and microRNAs(miRNAs) play important roles in NSCL/P. However, the potential regulatory associations remain largely unknown. In this study, we screened differentially expressed miRNAs and constructed competing endogenous RNA (ceRNA) networks to lay a foundation for further research on the regulatory mechanism of ncRNAs in NSCL/P. METHODS: NSCL/P plasma RNA was analyzed by miRNA sequencing. The bioinformatics database, GEO and STRING database, GO and KEGG enrichment analysis and Cytoscape software were used to analyze and screen lncRNAs and mRNAs potentially related to differential miRNAs. The expression levels of lncRNA, miRNA and mRNA in ceRNA network were detected by RT-qPCR. RESULTS: In NSCL/P plasma samples, there were 47 differentially expressed miRNAs in CPO group and 36 differentially expressed miRNAs in CL/P group. GO and KEGG enrichment analysis showed that cell cycle, cell response to DNA damage stimulation, and the TGF-ßsignaling pathway were relevant to the formation of NSCL/P. The RT-qPCR results showed that the expression levels of lncRNA NEAT1, hsa-miR-130 b-3p, hsa-miR-212-3p, hsa-miR-200 b-3p and SMAD2 were different in NSCL/P. CONCLUSIONS: We found that differentially expressed miR-212-3p, miR-200 b-3p and miR-130 b-3p may be involved in the pathogenesis of cleft palate by regulating related target genes.
