NRF2 promotes the migration of ovarian cancer cell lines by targeting TAGLN mediated epithelial-mesenchymal transition.

OBJECTIVE: Migration is one of the essential steps of cancer cell metastasis. Here we try to demonstrate the molecular crosstalk between NRF2-TAGLN pathway and ovarian cancer migration. METHODS: Western blot and Real-time PCR were used to determine the expression of NRF2 and TAGLN. Pharmacological treatment and gene intervention were employed to modulate gene expression. Wound-healing and Transwell assay were used to examine the migration ability of ovarian cancer cell lines. Dual luciferase activity and chromatin immunoprecipitation assay (CHIP) were applied to verify TAGLN as a NRF2 target gene. RESULTS: NRF2 overexpression promoted the migration of ovarian cancer cells. Our previous microarray data indicated 18 putative NRF2 target genes. Among these genes, TAGLN, binding with actin protein, has been reported to affect cytoskeletal dynamics and cell migration. A detailed analysis identified one functional antioxidant response element (ARE) in the promoter region of TAGLN, indicating TAGLN as one NRF2 target gene. Next, we explored the role of TAGLN on ovarian cancer cell migration. It showed that TAGLN overexpression promoted ovarian cancer cell migration. Conversely, knockdown of TAGLN inhibited ovarian cancer cell migration. Furthermore, transient knockdown of TAGLN using specific siRNA notably decreased cell motility in the NRF2 overexpressed ovarian cancer cells, significantly reversing the effect of NRF2 on ovarian cancer cell migration. Besides, NRF2 overexpression activated epithelial-mesenchymal transition (EMT) pathway. While, co-transfection TAGLN siRNA in NRF2 overexpressed cancer cells leaded to the upregulation of E-cadherin and the downregulation of N-cadherin, inactivating EMT pathway. CONCLUSIONS: Our study shows that NRF2 and the novel target gene TAGLN, plays a critical role in ovarian cancer cell migration via modulating cell motility and EMT. Targeting NRF2-TAGLN axis may be a new strategy to overcome metastasis and improve the ovarian cancer prognosis. CLINICAL TRIAL NUMBER: Not applicable.