Integrative analysis links autophagy to intrauterine adhesion and establishes autophagy-related circRNA-miRNA-mRNA regulatory network

Intrauterine adhesion (IUA) is a troublesome complication characterized with endometrial fibrosis after endometrial trauma. Increasing number of investigations focused on autophagy and non-coding RNA in the pathogenesis of uterine adhesion, but the underlying mechanism needs to be further studied.

In the current study, we firstly constructed autophagy-related circRNA-miRNA-mRNA regulatory network and identified hub ARCs and ARDEMs had not been reported in IUA.

mRNA expression profile and miRNA expression profile were obtained from Gene Expression Omnibus database. The autophagy related genes were low. Venn diagram was used to set the intersection of autophagy genes and DEGs to obtain ARDEGs. Circbank was used to select hub autophagy-related circRNAs based on ARDEMs. Then, the differentially expressed autophagy-related genes, miRNAs and circRNAs were analyzed by functional enrichment analysis, and protein-protein interaction network analysis. Finally, the expression levels of hub circRNAs and hub miRNAs were validated through RT-PCR of clinical intrauterine adhesion samples. In vitro experiments were investigated to explore the effect of hub ARCs on cell autophagy, myofibroblast transformation and collagen deposition.

11 autophagy-related differentially expressed genes (ARDEGs) and 41 differentially expressed miRNA (ARDEMs) compared between normal tissues and IUA were identified. Subsequently, the autophagy-related miRNA-mRNA network was constructed and hub ARDEMs were selected. Furthermore, the autophagy-related circRNA-miRNA-mRNA network was established. According to the ranking of number of regulated ARDEMs, hsa-circ-0047959, hsa-circ-0032438, hsa-circ-0047301 were regarded as the hub ARCs. In comparison of normal endometrial tissue, all three hub ARCs were upregulated in IUA tissue. All hub ARDEMs were downregulated except has-miR-320c. Conclusions: In the current study, we firstly constructed autophagy-related circRNA-miRNA-mRNA regulatory network and identified hub ARCs and ARDEMs had not been reported in IUA.