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

Aims: Previous 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 methods: We 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 findings: The 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 miR200a. 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. Significance: Our results provided a potential molecular mechanism by which miR-200a involved in hypoxiainduced metastasis and invasion in ovarian cancer, suggesting a possible target for the treatment of ovarian cancer.

Automated summary

This study revealed the crucial role of STAT4 in the metastasis and invasion of ovarian cancer, especially under hypoxic conditions. MiR-200a was identified as a direct regulator of STAT4, influencing the progression of EMT in ovarian cancer cells. These findings suggest a potential therapeutic target for the treatment of ovarian cancer.