PRMT1 potentiates chondrosarcoma development through activation of YAP activity.

Protein arginine methyltransferase 1 (PRMT1) is identified as an oncogene implicated in various types of human cancers, while Yes-associated protein (YAP) as a key transcriptional coactivator of the Hippo signaling plays a vital role in tissue homeostasis and tumorigenesis. To date, the underlying biological functions, prognostic values, and potential mechanisms of PRMT1 and YAP in chondrosarcoma development have not been clearly elucidated. Here, we show that upregulation of PRMT1 and YAP is significantly detected in human chondrosarcoma specimens. Elevated levels of PRMT1 positively correlated with YAP nuclear accumulation are significantly associated with high-grade chondrosarcoma and poor prognosis. Moreover, YAP is recognized as an independent prognostic factor for chondrosarcoma patients. Ectopic expression of PRMT1 potentiates, but depletion of PRMT1 attenuates, chondrosarcoma cell growth in vitro and in vivo. Mechanistically, we have discovered that PRMT1 functions upstream of LATS1 and suppresses LATS1-mediated phosphorylation of YAP (Ser127), and thus promotes chondrosarcoma cell survival in a YAP-dependent manner. Collectively, our study identifies PRMT1 as a positive regulator of YAP activity in chondrosarcoma, highlighting a novel therapeutic target against chondrosarcoma and other YAP-driven cancers.