PRMT5 activates KLF5 by methylation to facilitate lung cancer.

Abstract

The highly expressed oncogenic factor Krüppel-like factor 5 (KLF5) promotes various cancerous processes, such as cell growth, survival, anti-apoptosis, migration and metastasis, particularly in lung cancer. Nevertheless, the modifications to KLF5 after translation are poorly understood. Protein arginine methyltransferase 5 (PRMT5) is considered as an oncogene known to be involved in different types of carcinomas, including lung cancer. Here, we show that the expression levels of PRMT5 and KLF5 are highly expressed lung cancer. Moreover, PRMT5 interacts with KLF5 and facilitates the dimethylation of KLF5 at Arginine 41 in a manner that depends on methyltransferase activity. Downregulation or pharmaceutical suppression of PRMT5 reduces the expression of KLF5 and its downstream targets both in vitro and in vivo. Mechanistically, the dimethylation of KLF5 by PRMT5 promotes the maintenance and proliferation of lung cancer cells at least partially by stabilising KLF5 via regulation of the Akt/GSK3β signalling axis. In summary, PRMT5 methylates KLF5 to prevent its degradation, thereby promoting the maintenance and proliferation of lung cancer cells. These results suggest that targeting PRMT5/KLF5 axis may offer a potential therapeutic strategy for lung cancer.