The long noncoding RNA regulates myoblast plasticity and muscle regeneration through epithelial-mesenchymal transition.

Formation of skeletal muscle is among the most striking examples of cellular plasticity in animal tissue development, and while muscle progenitor cells are reprogrammed by epithelial-mesenchymal transition (EMT) to migrate during embryonic development, the regulation of EMT in post-natal myogenesis remains poorly understood. Here, we demonstrate that the long noncoding RNA (lncRNA) regulates EMT in myoblast differentiation and skeletal muscle regeneration. Chronic inhibition of in C2C12 myoblasts induced EMT, and suppressed cell state transitions required for differentiation. Furthermore, adenoviral knockdown compromised muscle regeneration, which was accompanied by abnormal mesenchymal gene expression and interstitial cell proliferation. Transcriptomic and pathway analyses of -depleted C2C12 myoblasts and injured skeletal muscle revealed a significant dysregulation of EMT-related genes, and identified TGFβ as a key upstream regulator. Importantly, inhibition of TGFβR1 and its downstream effectors, and the EMT transcription factor Snai2, restored many aspects of myogenic differentiation in -depleted myoblasts We further demonstrate that reduction of -dependent Ezh2 activity results in epigenetic alterations associated with TGFβ activation. Thus, regulates myoblast identity to facilitate progression into differentiation.