Respiratory Syncytial Virus Infection Induced Mucus Secretion by Down Regulation of miR-34b/c-5p Expression in Airway Epithelial Cells

Abstract

Background: Severe RSV infection is the main cause of hospitalization to children under age of five. The regulation of miRNAs on the severity of RSV infection are unclear. The aim of the study is to identify the critical differential expression miRNAs (DE miRNAs) that can regulate the pathological response in RSV-infected airway epithelial cells. Methods: miRNA and mRNA chips of RSV-infected airway epithelia from Gene Expression Omnibus (GEO) was screened and analyzed. DE miRNAs from different groups were identified and performed for further pathway and process enrichment analysis. DE miRNAs-targeted gene functional network was constructed based on miRNA-mRNA interaction. The screened critical miRNA was also investigated by bioinformatics analysis. Then, RSV-infected human bronchial epithelial cells (HBECs) were constructed to verify the expression of the DE miRNAs. Finally, specific synthetic DE miRNAs mimics was used to confirm effect of the DE miRNAs on the of RSV-infected HBECs. Results: 14 DE miRNAs were identified from GEO62306 dataset. Hsa-mir-34b/c-5p decreased significantly in HBECs after RSV infection. Consistent with the biometric analysis, hsa-mir-34b/c-5p is involved in the regulation of mucin expression gene MUC5AC. In RSV-infected HBECs, the inducement of MUC5AC production by decreased hsa-mir-34b/c-5p was partly mediated through activation of c-Jun. Conclusions: We conclude that the decreased expression of hsa-mir-34b/c-5p in HBECs after RSV infection play a critical role in MUC5AC expression through activation of c-Jun. These findings provide new insights into the mechanism of mucus obstruction after RSV infection and represent a useful biomarker of RSV infection and valuable targets of airway obstruction treatment. Funding Statement: This work was funded by grants #81970033，#31900424，#81570026, #81670002 and #3167188 from the NSFC; grants #2017JJ2402, #2019JJ50760 from the Hunan Natural Science Foundation; grant #16K097 from open Foundation of Hunan College Innovation Program and grant #2018zzts813, #2018zzts812, #2019zzts327, #2019zzts1008 from the Fundamental Research Funds for the Central Universities of Central South University. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: The authors stated: Not applicable.