Tumour metastasis is responsible for the vast majority of cancer-related deaths and is facilitated by epithelial-to-mesenchymal transition (EMT). A number of factors have been found to regulate EMT, including the ECM glycoprotein tenascin C (TNC), and several microRNAs, but the role of long non-coding (lnc)RNAs in EMT is less clear. In this study, Meera Saxena, Gerhard Christofori and co-workers (Saxena et al., 2021) set out to identify lncRNAs involved in the process by inducing EMT in normal murine mammary gland cells and sequencing the generated RNA species over a time course of up to 10 days. Among the sequenced transcripts, they found 114 lncRNAs whose presence is associated with EMT, with only a few of those having previously been implicated in EMT. The authors then focused on ET-20, as it maps in antisense orientation to the Tnc gene, and show that it is co-regulated with Tnc by Sox4, an EMT master transcription factor. Accordingly, ET-20 ablation blocks Tnc expression, as well as the induction of EMT. With regard to the underlying mechanism, the authors describe that ET-20 interacts with desmosomal proteins at the cell membrane; this disrupts desmosomes, and so promotes loss of adhesion and, subsequently, EMT. Finally, they confirm a similar role in EMT for a human ET-20 variant, suggesting that this lncRNA might constitute a valuable therapeutic target or prognostic biomarker for invasive breast cancers.
ET-20, a long non-coding RNA involved in EMT
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ET-20, a long non-coding RNA involved in EMT. J Cell Sci 1 November 2021; 134 (21): e134_e2101. doi:
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