Overexpression of STAT4 under hypoxia promotes EMT through miR-200a/STAT4 signal pathway

Abstract

AimsPrevious reports have found that STAT4 is involved in the epithelial-mesenchymal transition (EMT), thereby regulating the metastasis and invasion of ovarian cancer. However, the mechanisms underlying remain unclear. Main methodsWe first established hypoxia-induced in vivo and in vitro models. The expression levels of signal transducer and activator of transcription 4 (STAT4), the markers of EMT and microRNA-200a (miR-200a) were assessed by western blot and qRT-PCR analysis, respectively. Through the bioinformatics analysis and luciferase assay, the relationship between miR-200a and SATA4 was performed. The gain- and loss-function experiments were performed to examine the role of miR-200a/STAT4 axis. Key findingsThe results showed that the protein level of STAT4 was significantly up-regulated in our hypoxia-exposed models, and contributed to the regulating of EMT. Besides, we found STAT4 was a direct target of miR-200a. Overexpression of miR-200a repressed the expression of STAT4, and inhibited EMT progress, whereas the silencing of miR-200a promoted the STAT4-mediated EMT regulation both in vitro and in vivo. SignificanceOur results provided a potential molecular mechanism by which miR-200a involved in hypoxia-induced metastasis and invasion in ovarian cancer, suggesting a possible target for the treatment of ovarian cancer.