Jianhua Wu,Lizhen Wu,Li Zhang,Huanhuan Xu,Min Wang,Lin Wang,Jie Chen,Kaiyue Sun
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 may relieve AR by negatively regulating TLR4/MyD88/NF-κB pathway, indicating that miR-224-5p may be a promising target for AR treatment.
Wang Yichao,Wang Pan,Zhao Lei,Chen Xiaoying,Lin Zhu,Zhang Ling,Li Zhaoyun
Objective: In this study, we focused on the potential mechanism of miRNAs carried by human umbilical cord mesenchymal stem cells-derived exosomes (hUCMSCs-exo) in breast cancer (BC).Methods: RT-qPCR was conducted for the expression of miR-224-5p and HOXA5 in tissues and cells. After co-culture of exosomes and MCF-7 or MDA-MB-231 cells, the cell proliferation was observed by MTT and cell colony formation assay, while apoptosis was measured by flow cytometry. In addition, the expression of HOXA5 and autophagy pathway-related proteins LC3-II, Beclin-1 and P62 was detected by western blotting. And immunofluorescence was applied for detection of LC3 spots. The binding of miR-224-5p to HOXA5 was verified by the luciferase reporter gene assay and RNA-binding protein immunoprecipitation assay. Finally, in vivo experiment was performed to investigate the effect of miR-224-5p on BC growth.Results: MiR-224-5p was up-regulated and HOXA5 was down-regulated in BC tissues and cells. HOXA5 was confirmed to be the target gene of miR-224-5p. MiR-224-5p carried by hUCMSCs-exo was able to promote the proliferation and autophagy of BC cells, while inhibited apoptosis. Bases on xenograft models in nude mice, it was also revealed that miR-224-5p carried by hUCMSCs-exo could regulate autophagy and contribute to the occurrence and development of BC in vivo.Conclusion: MiR-224-5p carried by hUCMSCs-exo can regulate autophagy via inhibition of HOXA5, thus affecting the proliferation and apoptosis of BC cells.
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