慢性鼻窦炎伴鼻息肉的候选竞争性内源RNA网络研究OA

OBJECTIVE To construct a candidate lncRNA-miRNA-mRNA competing endogenous RNA(ceRNA)regulatory network in chronic rhinosinusitis with nasal polyps(CRSwNP)and to validate the expression changes of key miRNAs in nasal polyp tissue,thereby providing a basis for elucidating the pathogenesis of CRSwNP and identifying candidate molecular markers.METHODS Three sequencing datasets(GSE136825,GSE36830 and GSE72713)from the Gene Expression Omnibus(GEO)database were integrated.Following background correction,normalization and batch-effect adjustment,the Limma and EdgeR algorithms were used to screen differentially expressed lncRNAs,miRNAs and mRNAs between nasal polyp tissue and normal uncinate process mucosa.The miRWalk 3.0 and StarBase v3.0 databases were used to predict RNA targeting interactions,and the ceRNA regulatory network was constructed with Cytoscape.Nasal polyp tissues from 6 patients with CRSwNP and uncinate process mucosa from 5 healthy subjects were collected,and the expression levels of candidate miRNAs were validated by RT-qPCR.RESULTS A total of 77 differentially expressed lncRNAs(20 upregulated and 57 downregulated)and 23 intersectant differentially expressed miRNAs were identified.Seven lncRNAs,including SRGAP3-AS2,DLX6-AS1 and ACTA2-AS1,showed high-confidence predicted targeting interactions with seven miRNAs,including hsa-miR-378h and hsa-miR-4434.The resulting candidate ceRNA regulatory network comprised 156 nodes and 158 interaction edges,in which ACTA2-AS1 showed the highest binding score with hsa-miR-378h.RT-qPCR revealed that,compared with the healthy control group,hsa-miR-4434 was significantly upregulated(P<0.01)and hsa-miR-378h significantly downregulated(P<0.05)in CRSwNP tissue,whereas the remaining four miRNAs showed no significant difference.CONCLUSION This study constructed a candidate ceRNA regulatory network containing seven miRNAs not previously reported in CRSwNP,and confirmed dysregulated expression of hsa-miR-4434 and hsa-miR-378h in clinical tissue,suggesting that these two miRNAs may participate in the pathogenesis of CRSwNP and merit further evaluation as potential molecular markers.As the regulatory relationships in the network were derived from database prediction,their functional and causal roles require further validation in vitro and in vivo.