BackgroundCircular RNAs (circRNAs) play an essential role in developing tumors, but their role in non-small cell lung cancer (NSCLC) is unclear. Thus, the present study explored the possible molecular mechanism of circRNAs in NSCLC.MethodsThree circular RNA (circRNA) microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differential expressions of circRNAs (DECs) were identified in NSCLC tissue and compared to adjacent healthy tissue. The online cancer-specific circRNA database(CSCD) was used for the analysis of the DECs function. Protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Cytoscape and UALCAN were used to predict the critical nodes and perform patient survival analysis, respectively. The interaction between the DECs, the predicted miRNAs, and hub genes was also determined. Finally, the circRNA-miRNA-mRNA network was established.ResultsThe expression of hsa_circ_0049271, hsa_circ_0026337, hsa_circ_0043256, and hsa_circ_0008234 was decreased in NSCLC tissues. The Encyclopedia of RNA Interactomes (ENCORI) and CSCD database results showed that hsa_circ_0026337 was found to sponge with miR-1193, miR-197-3p, miR-3605-5p, miR-433-3p and miR-652-3p, and hsa_circ_0043256 to sponge with miR-1252-5p, miR-494-3p and miR-558 respectively. Subsequently, 100 mRNAs were predicted to bind with these seven miRNA response elements (MREs). The GO analysis and KEGG pathway revealed that these 100 MREs might be involved in “histone deacetylase binding” and “cellular senescence”. PPI network and Cytoscape identified the top ten hub genes. Survival analysis data showed that the low expression of hsa_circ_0026337 was significantly associated with shortened survival time in NSCLC (P=0.037) ,which increased the expression level of hsa-miR-197-3p, thereby inhibiting the translation of specific proteins.ConclusionThis study examined the circRNA-miRNA-mRNA regulatory network associated with NSCLC and explored the potential functions of DECs in the network to elucidate the mechanisms underlying disease progression in NSCLC.

Background Exosome from adipose-derived stem cells (ADSCs-Exo) has been shown to inhibit the progression of human diseases, including sepsis-related acute kidney injury (AKI). CircVMA21 is considered to be an important regulator for sepsis-related AKI. However, whether ADSCs-Exo affected sepsis-induced AKI by delivering circVMA21 is not clear. Methods ADSCs was identified by alizarin red staining, oil red O staining, and flow cytometry. ADSCs-Exo was authenticated by transmission electron microscopy, nanoparticle tracking analysis, western blot analysis, and immunofluorescence assay. Cell apoptosis was assessed by flow cytometry, and inflammation cytokine levels were determined by ELISA. Lactate production was assessed using Lactate Acid Content Assay Kit. The expression levels of aerobic glycolysis-related markers, circVMA21 and miR-16-5p were evaluated by qRT-PCR. Dual-luciferase reporter assay and RIP assay were employed to detect RNA interaction. Animal experiments were used to evaluate the role of ADSCs-Exo on renal function and cell injury in LPS-induced AKI mice model. Results ADSCs-Exo inhibited LPS-induced HK-2 cell apoptosis, inflammation and aerobic glycolysis. Knockdown of exosomal circVMA21 derived from ADSCs enhanced HK-2 cell injury induced by LPS. In terms of mechanism, circVMA21 could serve as sponge for miR-16-5p. Besides, miR-16-5p inhibitor reversed the promotion effect of Exo-sh-circVMA21 on LPS-induced cell injury. In addition, ADSCs-Exo protected LPS-induced AKI in mice by increasing circVMA21 expression and decreasing miR-16-5p expression. Conclusion Exosomal circVMA21 derived by ADSCs relieved LPS-induced AKI through targeting miR-16-5p, which provided a potential molecular target for treating sepsis-related AKI.