MiR-199a-3p/5p participated in TGF-β and EGF induced EMT by targeting DUSP5/MAP3K11 in pterygium

Autor:	Chen Qiao, Ming Yan, Shuai Zhang, Shiqi Dong, Guohua Yang, Chen Wang, Fang Zheng, Siying He, Yuting Xu, Huang Yifang
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	0301 basic medicine Epithelial-Mesenchymal Transition lcsh:Medicine DUSP5 Pterygium General Biochemistry Genetics and Molecular Biology miR-199a Flow cytometry 03 medical and health sciences 0302 clinical medicine Western blot Transforming Growth Factor beta Epidermal growth factor microRNA medicine MAP3K11 Humans Epidermal Growth Factor medicine.diagnostic_test Chemistry Research lcsh:R EMT Cell migration General Medicine MicroRNAs 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Cancer research Dual-Specificity Phosphatases Immunohistochemistry Transforming growth factor
Zdroj:	Journal of Translational Medicine, Vol 18, Iss 1, Pp 1-19 (2020) Journal of Translational Medicine
ISSN:	1479-5876
DOI:	10.1186/s12967-020-02499-2
Popis:	Background Recently, it has been reported that miRNA is involved in pterygium, however the exact underlying mechanism in pterygium is unrevealed and require further investigation. Methods The differential expression of miRNA in pterygium was profiled using microarray and validated with quantitative real-time polymerase chain reaction (qRT-PCR). Human conjunctival epithelial cells (HCEs) were cultured and treated with transforming growth factor β (TGF-β) and epidermal growth factor (EGF) and transfected with miR-199a-3p/5p mimic and inhibitor. Markers of epithelial-mesenchymal transition (EMT) in HCEs were detected using western blot and immunohistochemistry. Cell migration ability was determined using wound healing and transwell assay, while apoptosis was determined by flow cytometry. The target genes of miR-199a were confirmed by the dual-luciferase reporter assay. Results TGF-β and EGF could induced EMT in HCEs and increase miR-199a-3p/5p but suppress target genes, DUSP5 and MAP3K11. With the occurrence of EMT, cell migration ability was enhanced, and apoptosis was impeded. Promoting miR-199a-3p/5p expression could induce EMT in HCEs without TGF-β and EGF, while suppressing miR-199a-3p/5p could inhibit EMT in TGF-β and EGF induced HCEs. In a word, TGF-β and EGF induced EMT could be regulated with miR-199a-3p/5p-DUSP5/MAP3K11 axes. The validated results in tissues showed that, compared with control conjunctival tissues, miR-199a-3p/5p were more overexpressed in pterygium, while DUSP5/MAP3K11 were lower expressed. In addition, bioinformatics analysis indicated the miR-199a-3p/5p-DUSP5/MAP3K11 was belong to MAPK signalling pathway. Conclusions TGF-β and EGF induce EMT of HCEs through miR-199a-3p/5p-DUSP5/MAP3K11 axes, which explains the pathogenesis of EMT in pterygium and may provide new targets for pterygium prevention and therapy.
Databáze:	OpenAIRE
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