Spatiotemporal regulation of myocardin is essential for non-small cell lung cancer metastasis

Abstract

Myocardin is known as an important transcriptional regulator in smooth and cardiac muscle development as well as a tumor suppressor. However, the pathological function of myocardin in NSCLC metastasis is poorly understood. Here, we have described novel roles for myocardin in the metastatic cascade using in vitro and in vivo models. We demonstrate that myocardin deficiency is sufficient to trigger epithelial–mesenchymal transition (EMT) process but reduces metastatic potential of NSCLC in vivo. Myocardin deficiency reduces lung cancer metastasis because of persistent EMT and decreasing colonization capacity. Restoring myocardin expression in colonization stage promotes the metastasis of lung cancer cells. An epigenetically negative feedback loop formed by myocardin and PRMT5/MEP50 complex prevents EMT. We also uncover the unknown mechanism of myocardin suppression in lung cancer tissues that PRMT5/MEP50 complex negatively regulates myocardin expression. It helps to reconcile conflicting results that have challenged the significance of EMT and cancer metastasis and explain the phenotype of myocardin suppression in lung cancer cells.

Keywords

• Myocardin
• EMT
• Metastasis
• NSCLC