RAE1 mediated ZEB1 expression promotes epithelial–mesenchymal transition in breast cancer

Abstract

Breast cancer metastasis accounts for most of the deaths from breast cancer. Since epithelial-mesenchymal transition (EMT) plays an important role in promoting metastasis of cancer, many mechanisms regarding EMT have been studied. We previously showed that Ribonucleic acid export 1 (RAE1) is dysregulated in breast cancer and its overexpression leads to aggressive breast cancer phenotypes by inducing EMT. Here, we evaluated the functional capacity of RAE1 in breast cancer metastasis by using a three-dimensional (3D) culture system and xenograft models. Furthermore, to investigate the mechanisms of RAE1-driven EMT, in vitro studies were carried out. The induction of EMT with RAE1-overexpression was confirmed under the 3D culture system and in vivo system. Importantly, RAE1 mediates upregulation of an EMT marker ZEB1, by binding to the promoter region of ZEB1 . Knockdown of ZEB1 in RAE1-overexpressing cells suppressed invasive and migratory behaviors, accompanied by an increase in epithelial and a decrease in mesenchymal markers. Taken together, these data demonstrate that RAE1 contributes to breast cancer metastasis by regulating a key EMT-inducing factor ZEB1 expression, suggesting its potential as a therapeutic target.

E-cadherin, Snail, ZEB-1, DNMT1, DNMT3A and DNMT3B expression in normal and breast cancer tissues*

“…ZEB-1 is another EMT-related gene which acts as a tumor suppressor and its expression is related to inhibition of cancerous conditions (Zhang et al, 2018). One of the oncogenes, named Ribonucleic acid export 1 (RAE1), is over-expressed in breast cancer due to changes in the level of ZEB-1 (Oh et al, 2019). Yu and others (Yu et al, 2018) documented that the hTERT promoter is stimulated by ZEB-1, leading to triggering of a sequence of breast cancer-related signaling pathways.…”

Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex

“…RAE1 and NUP98, which are kinetically partitioned among other components in both cytoplasmic and nuclear compartments, also act as regulators for BMAL1 shuttling between the cytoplasm and nucleus, as well as maintenance of the correct pace of the circadian clock [ 16 ]. In addition, RAE1 was found to mediate ZEB1 expression by promoting epithelial-mesenchymal transition in breast cancer [ 17 ].…”

A multi-omic dissection of super-enhancer driven oncogenic gene expression programs in ovarian cancer

“…We identified one cis direct target gene and four cis indirect target genes for SE60 (Figure 6B). Of note, the cis direct target gene for SE60, RAE1, has previously been associated with Invasion in ovarian cancer and has been shown to promote EMT in breast cancer 54 . In addition, increased expression of this gene portends a worse outcome in HGSOC patients (Figure 6C and D).…”

“…This method was used to detect significant enrichments in the ChIP/IP data file when compared to the Input data file or relative to neighboring background regions. ___________________________________________________________________________ 54 Regions was necessary because the locations and lengths of Intervals are rarely exactly the same when comparing different samples. Furthermore, with this approach fragment density values could be obtained even for samples for which no peak was called.…”