Protein arginine methylation, which is mediated by the protein arginine methyltransferases (PRMTs), is associated with numerous fundamental cellular processes. Our previous studies have shown that PRMT1 activated Hedgehog signaling in the esophageal squamous cell carcinoma (ESCC) cells and promoted the growth and migration of cancer cells. However, the detailed mechanisms are unknown. In this study, it was found that PRMT1 interacted with the transcriptional factor Gli1 (glioma-associated oncogene homolog 1) in ESCC cells. The DNA-binding domain (DBD) of Gli1 is responsible for its interaction with PRMT1. Moreover, PRMT1 promoted the methylation of Gli1, and knocking down the expression of PRMT1 impaired the transcriptional activity as well as the biological functions of Gli1. Taken together, our study demonstrated that PRMT1 is a positive regulator of Hedgehog signaling, and PRMT1 might be a therapeutic target for ESCC.
PRMT1 Gli1 Methylation ESCC
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Briscoe J, Therond PP, The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol. 2013;14(7):416–29.CrossRefPubMedGoogle Scholar
Zhu W et al. Correlation of hedgehog signal activation with chemoradiotherapy sensitivity and survival in esophageal squamous cell carcinomas. Jpn J Clin Oncol. 2011;41(3):386–93.CrossRefPubMedGoogle Scholar
Min S et al. The glioma-associated oncogene homolog 1 promotes epithelial—mesenchymal transition in human esophageal squamous cell cancer by inhibiting E-cadherin via Snail. Cancer Gene Ther. 2013;20(7):379–85.CrossRefPubMedGoogle Scholar
Isohata N et al. Hedgehog and epithelial-mesenchymal transition signaling in normal and malignant epithelial cells of the esophagus. Int J Cancer. 2009;125(5):1212–21.CrossRefPubMedGoogle Scholar