TRIM37 interacts with PTEN to promote progression of hepatocellular carcinoma cells by modulating AKT/GSK-3β/β-Catenin pathway.

Background: Tripartite motif-containing 37 protein (TRIM37), a member of the TRIM protein family, functions as an E3 ubiquitin ligase. It was implicated in the pathogenesis of numerous malignancies. Nonetheless, its precise function in hepatocellular carcinoma (HCC) is still insufficiently understood. This study aims to elucidate the regulatory function of TRIM37 in HCC progression and to explore the underlying molecular mechanisms. Methods: Immunohistochemistry (IHC) and reverse transcription quantitative real time polymerase chain reaction (qRT-PCR) were conducted to estimate TRIM37 concentrations in HCC cell lines. Notably, HCCLM3 and Huh7 cell lines were utilized to establish models of TRIM37 upregulation and downregulation, respectively. Cell Counting Kit-8 (CCK-8), colony formation, and Transwell assessments were carried out to observe the TRIM37 effects on cellular growth and invasion. The expression of proteins linked to the AKT/GSK-3β/β-Catenin signaling pathways and epithelial-mesenchymal transition (EMT) was assessed using Western blot (WB). In addition, ubiquitination assays and co-immunoprecipitation (Co-IP) tests were performed to examine the TRIM37-PTEN association and the ubiquitination status of PTEN. Results: Significant TRIM37 overexpression was shown in HCC tissues and cell lines. Functional analyses demonstrated that TRIM37 promotes cell proliferation and invasion. Further analyses showed that TRIM37 enhances these malignant behaviors by promoting PTEN degradation through ubiquitination, thereby stimulating the AKT/GSK-3β/β-Catenin pathway. Conclusions: TRIM37-triggered post-translational modification of PTEN via ubiquitination may have a vital function in promoting HCC progression. These findings suggest that targeting the TRIM37/PTEN/AKT/GSK-3β/β-Catenin axis may offer a promising therapeutic approach for the management of HCC.