A core microRNA signature associated with inducers of the epithelial-to-mesenchymal transition

Abstract

Although it is becoming clear that certain miRNAs fulfil a fundamental role in the regulation of the epithelial-to-mesenchymal transition (EMT), a comprehensive study of the miRNAs associated with this process has yet to be performed. Here, we profiled the signature of miRNA expression in an in vitro model of EMT, ectopically expressing in MDCK cells one of seven EMT transcription factors (SNAI1, SNAI2, ZEB1, ZEB2, TWIST1, TWIST2 or E47) or the EMT inducer LOXL2. In this way, we identified a core subset of deregulated miRNAs that were further validated in vivo, studying endometrial carcinosarcoma (ECS), a tumour entity that represents an extreme example of phenotypic plasticity. Moreover, epigenetic silencing through DNA methylation of miRNA genes of the miR-200 family and miR-205 that are down-regulated during EMT was evident in both the in vitro (MDCK transfectants) and in vivo (ECS) models of EMT. The strong correlation between expression and DNA methylation suggests a major role for this epigenetic mark in the regulation of the miR-141-200c locus.

Whole-Genome DNA Methylation Profiling Identifies Epigenetic Signatures of Uterine Carcinosarcoma

“…This was highlighted by several DMRs targeting the MIR200 family (MIR200a, MIR200b, MIR200c, MIR141, MIR429) in UCS [43]. We found that CADs were located in MIR200b-MIR200a-MIR429’s promoter region (4 kb upstream of MIR200b), whereas in MIR200c-MIR141, SADs were localized in enhancer regions as predicted by chromHMM [41] (Figure 7 A ).…”

Rab25 acts as an oncogene in luminal B breast cancer and is causally associated with Snail driven EMT

“…Molecularly, these cells are similar to basal breast cancer cells, originating from the same precursor [53]. However, with over expression of Snail, they manifest a claudin-low phenotype with upregulation of epithelial to mesenchymal (EMT) features [55, 56]. These cells with negligible expression of claudin 3, 4 or 7 and E-cadherin [49], are widely used to study EMT and known to cluster with the claudin-low patients and cell lines [55, 56].…”

“…However, with over expression of Snail, they manifest a claudin-low phenotype with upregulation of epithelial to mesenchymal (EMT) features [55, 56]. These cells with negligible expression of claudin 3, 4 or 7 and E-cadherin [49], are widely used to study EMT and known to cluster with the claudin-low patients and cell lines [55, 56]. Here we found that while parental HMLE cells (clusters with basal/basal A) have Rab25 protein expression, the introduction of Snail completely suppresses Rab25 protein (Figure 3C upper panel).…”

DNA Methylation-mediated Repression of miR-941 Enhances Lysine (K)-specific Demethylase 6B Expression in Hepatoma Cells

“…The epithelial to mesenchymal transition (EMT) is an important cellular phenotypic change in which polarized, immotile epithelial cells acquire the motile mesenchymal phenotype. EMT is regulated by miRNAs (12,13) that promote tumor invasion and metastasis and allow tumor cells to escape apoptosis (14).…”