USP37 facilitates hepatocellular carcinoma progression by deubiquitinating RAF1 and activating ERK1/2 signaling.

USP37 plays a pivotal role in cell cycle regulation, oncogenesis and metastasis. So far, the precise mechanisms and function of USP37 in hepatocellular carcinoma (HCC) remain unclear. In this study, we found USP37 expression was significantly elevated in HCC tissues compared to adjacent normal tissues and high expression was negatively correlated with patient prognosis. Functional assays including CCK-8, EdU staining, colony formation assays, patient derived organoids, transwell assays, wound healing, and in vivo models demonstrated that USP37 significantly promoted proliferation and migration of HCC cells. Mechanistically, USP37 interacted with RAF1, enhancing its protein stability and activating the ERK signaling pathway. This study identifies a novel mechanism by which USP37 promotes HCC cell proliferation through stabilizing RAF1 and activating the RAF-ERK signaling pathway. These findings highlight USP37 as a potential therapeutic target for HCC.