The SAM-pointed domain-containing ETS transcription factor (SPDEF) is an epithelial-specific transcription factor of the E26 transformation-specific (ETS) family, which binds the target gene through the high-affinity sequence of GGAT. It is suggested that SPDEF targets the promoter activity of Forkhead Box M1 (FoxM1), which has been proven to be highly expressed in gastric cancer. We found that SPDEF was overexpressed both at the messenger RNA (mRNA) and at the protein level in human gastric cancer species. The gastric cancer cells transfected with the SPDEF expression plasmid or SPDEF small interfering RNA (siRNA) led to observations on the clone genetics assay that indicated the promotion or the inhibition of gastric cancer cell proliferation, respectively. Both mRNA and protein levels of FoxM1 were regulated by SPDEF in gastric cancer cells and FoxM1 was also overexpressed in the corresponding human gastric cancer species. The overexpression and inhibition of FoxM1 could upregulate and downregulate the mRNA and protein levels of SPDEF expression, respectively. The recovery experiments verified that the overexpression of FoxM1 could at least partially revert both the expression of SPDEF and the proliferation of the cell lines even with the siRNA inhibition of SPDEF. The result of the dual luciferase activity assay showed that SPDEF bound to the promoter of FoxM1 and activated it. FoxM1 might also bind to the promoter of SPDEF to affect its expression. The results were checked in vivo. In conclusion, SPDEF is overexpressed in gastric cancer, which can form a positive regulation loop with FoxM1 to promote gastric carcinogenesis.
Inflammatory allergic reaction is the main cause of allergic rhinitis (AR). Previous studies indicated that miR-224-5p was downregulated in the nasal mucosa of patients with AR, while the function of miR-224-5p in AR remains unclear. To explore this issue, AR mouse model was established using ovalbumin (OVA). For treatment group, lentivirus (LV)-miR-224-5p or its control was intranasally administrated to AR mice. miR-224-5p expression was detected by reverse transcription-quantitative PCR, followed by assessing the immunoglobulin E (IgE) level. Pathological alterations in nasal mucosa were detected using Hematoxylin-Eosin staining and Sirius red staining, followed by assessing the levels of inflammatory cells and factors. The NLRP3 inflammasome and TLR4/MyD88/NF-κB pathway were measured by Western blot, and then the relationship between miR-224-5p and toll-like receptor 4 (TLR4) was verified. The results showed that miR-224-5p was significantly decreased in nasal mucosa of AR mice. AR mice exhibited increased sneezing and nasal rubbing events, IgE level in serum, and pathological alterations in nasal mucosa, while overexpression of miR-224-5p markedly attenuated these changes. The levels of inflammatory cells in nasal lavage fluid and pro-inflammatory factors in serum and nasal mucosa were significantly increased in AR mice, which were reduced by miR-224-5p overexpression. Of note, LV-miR-224-5p treatment remarkably suppressed the activations of NLRP3 inflammasome and the TLR4/MyD88/NF-κB pathway in AR mice. Furthermore, miR-224-5p could bind to 3'-untranslated region (3'-UTR) of TLR4 and negatively regulate TLR4 level. Overall, we conclude that miR-224-5p 3 may relieve AR by negatively regulating TLR4/MyD88/NF-κB pathway, indicating that miR-224-5p may be a promising target for AR treatment.
<b><i>Introduction:</i></b> The study of peripheral circular RNA (circRNA) expression profile in patients with allergic rhinitis (AR) was absent to date, and we aimed to obtain the circRNA expression profile and identify the candidate biomarker from AR. <b><i>Methods:</i></b> circRNA chip was performed to screen differentially expressed circRNAs in the peripheral blood sample from AR patients and healthy controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed to further search the function of the differential expressed circRNAs. The real-time quantitative reverse transcription-polymerase chain reaction was further used to verify the candidate circRNA and also analyze its potential correlation with clinical parameters. <b><i>Results:</i></b> Significantly up-regulated expression level of hsa_circRNA_404013 in AR was obtained by circRNA chip and further verified in 79 AR patients and 48 healthy controls. hsa_circRNA_404013 was significantly positively correlated with nasal discharge, nasal itching, the total nasal symptoms of AR, and brain-derived neurotrophic factor (BDNF) expression level in peripheral blood. Receiver operating characteristic curve analysis results showed that hsa_circRNA_404013 may be used as peripheral blood circulating marker for the diagnosis of AR with the area under curve of 0.8499 (95% CI: 0.783–0.916). In further bioinformatics analysis, hsa_circRNA_404013 may regulate the expression of BDNF through hsa-mir-182-5p contributing to the pathogenesis of AR. <b><i>Conclusion:</i></b> The expression profile of circRNAs from the peripheral blood sample of AR patients was obtained. The expression of hsa_circRNA_404013 was significantly up-regulated in the peripheral blood of AR patients, which may be used as a circulating marker for AR patients. Furthermore, hsa_circRNA_404013 may regulate the expression level of BDNF through hsa-mir-182-5p in AR pathogenesis.
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