Abstract
Tripartite motif-containing 50 (TRIM50) belongs to the tripartite motif (TRIM) protein family, which has been implicated in the pathogenesis of multiple cancers. However, the role of TRIM50 in hepatocellular carcinoma (HCC) remains to be clarified. Here we showed that TRIM50 expression was significantly decreased in liver cancer tissues compared with corresponding non-cancerous liver tissues, and its decreased expression was significantly correlated with advanced disease progression. Gain-of-function assay by exogenous overexpression of TRIM50 in HCC cells showed that proliferation, colony formation, migration and invasion of HCC cells were significantly inhibited, whereas loss-of-function assay by TRIM50 knockdown showed that these malignant behaviors of HCC cells were significantly increased. Further investigation showed that TRIM50 could directly bind with SNAIL and induced K-48 linked poly-ubiquitous degradation of SNAIL protein, which further reversed SNAIL-mediated epithelial-to-mesenchymal transition (EMT) process of HCC cells. In vivo assay by xenograft tumor model verified the antitumor effect of TRIM50 on HCC. Taken together, these results showed that TRIM50 acted as a tumor suppressor in HCC cells by directly targeting SNAIL and reversing EMT, which further indicated that positive modulation of TRIM50 might be a novel therapeutic strategy for SNAIL overexpressed HCC cells.
Highlights
Hepatocellular carcinoma (HCC) is the primary malignancy of the liver and the third leading cause of cancerrelated death worldwide[1,2,3]
To explore whether expression of Tripartite motif-containing 50 (TRIM50) in HCC tissues was altered during the development of liver cancer, we detect the levels of TRIM50 in HCC tissues and corresponding non-cancerous liver tissues by immunohistochemistry (IHC), quantitative real-time polymerase chain reaction, and western blot
These data indicated that TRIM50 was downregulated in HCC tissues and its decreased expression contributed to HCC progression
Summary
Hepatocellular carcinoma (HCC) is the primary malignancy of the liver and the third leading cause of cancerrelated death worldwide[1,2,3]. Identifying novel disease marker and clarifying the pathological mechanism will provide new insight into this disease and facilitate discovery of novel therapeutic strategies. The role of tripartite motif (TRIM) proteins in the development of cancer has attracted much research interest, and novel tumor promoters and tumor suppressors have been identified in TRIM family members[4,5]. TRIM protein family includes >70 highly conserved proteins, which are usually composed of a RING (R) domain, one or two B-boxes (B) domain(s) and a predicted coiled coil (CC) domain[6,7]. TRIM proteins have been reported to play important roles in development, inflammation, anti-virus immunity and cancer[8]. Several TRIM family members were identified to play important roles in the development of liver cancer, which demonstrated that they might have potential applications as novel therapeutic targets or prognostic markers
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