Dysregulated YY1/PRMT5 axis promotes the progression and metastasis of laryngeal cancer by targeting Hippo pathway

Metastases lead to high mortality in laryngeal cancer, but the regulation of its underlying mechanisms remains elusive. We identified Protein arginine methyltransferase 5 (PRMT5) was significantly up-regulated in laryngeal cancer tissues, which predicts poor patient prognosis. Functional assays demonstrated that PRMT5 overexpression promoted the invasive capacity and lymph node metastasis in vitro and in vivo. Mechanistic experiments suggested that LATS2 was a downstream target of PRMT5. PRMT5 inhibition increased the expression of LATS2 and YAP phosphorylation in laryngeal cancer cells, thereby promoting laryngeal cancer metastasis. Furthermore, informatics and experimental data confirmed that PRMT5 gene was transcriptionally activated by YY1. Collectively, our results unravelled the important role of PRMT5 in laryngeal cancer tumorigenesis and metastasis. The dysregulation YY1/PRMT5/LATS2/YAP axis may contribute to laryngeal cancer progression; thus, PRMT5 may be a potential therapeutic strategy for patients with laryngeal cancer.

Automated summary

PRMT5 is significantly up-regulated in laryngeal cancer tissues, predicting poor patient prognosis; PRMT5 overexpression promotes the invasive capacity and lymph node metastasis in vitro and in vivo by increasing LATS2 expression and YAP phosphorylation; dysregulation of the YY1/PRMT5/LATS2/YAP axis may contribute to laryngeal cancer progression.