Research ArticleCancer

The lncRNA H19 mediates breast cancer cell plasticity during EMT and MET plasticity by differentially sponging miR-200b/c and let-7b

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Sci. Signal.  13 Jun 2017:
Vol. 10, Issue 483, eaak9557
DOI: 10.1126/scisignal.aak9557

A noncoding mediator of metastasis

To metastasize, cancer cells undergo dynamic shifts in phenotype called epithelial-to-mesenchymal transition (EMT) and its reverse process (MET). These phenotypic shifts are controlled in part by microRNAs (miRNAs), which, by binding to target transcripts, suppress the abundance of various proteins. By isolating tumor cells from the primary site, the circulation, and metastatic nodules in the lung in a mouse model of metastatic breast cancer, Zhou et al. found that the long noncoding RNA (lncRNA) H19 acted as a “sponge” for miRNAs to promote an epithelial or mesenchymal switch in tumor cells. In epithelial-like tumor cells in the primary and metastatic sites, H19 sequestered miR-200b/c, which ultimately inhibited the migration-related protein ARF. In mesenchymal-like, disseminated cells in the circulation, H19 sequestered let-7b, ultimately activating ARF. H19 abundance was greater in metastatic than in nonmetastatic human tumors. These findings reveal a previously unknown mediator of the EMT/MET phenomenon in metastasis.