PDLIM2 prevents the malignant phenotype of hepatocellular carcinoma cells by negatively regulating β-catenin

Hepatocellular carcinoma (HCC) is one of the most common malignancies and leading causes of cancer-related deaths globally. Despite significant advances in therapy, the molecular mechanisms underlying HCC development and progression remain unclear. Here, we aimed to explore the potential role of PDLIM2 in the development and epithelial-mesenchymal transition (EMT) of HCC via a possible modulation of beta-catenin. We first confirmed that PDLIM2 was downregulated in HCC tissues and cells and found lower PDLIM2 expression was associated with worse prognosis in HCC patients. Loss- and gain- of function experiments were performed to evaluate the roles of PDLIM2 and beta-catenin in HCC cell proliferation, migration, invasion, EMT, and colony formation. EMT was determined based on the levels of E-cadherin, zonula occludens-1, N-cadherin, and vimentin expression. In vivo, the roles of PDLIM2 and beta-catenin in HCC were investigated by using a nude mouse xenograft model. It should be noted that PDLIM2 led to the inhibition of beta-catenin activity and its downstream gene expression. Importantly, ectopic PDLIM2 expression inhibited the proliferation, migration, invasion, and EMT of HCC cells by reducing beta-catenin expression both in vitro and in vivo, thereby suppressing the occurrence and progression of HCC. Taken together, our results demonstrated that overexpressed PDLIM2 exerts a tumor-suppressive role in HCC by regulating beta-catenin. This study suggests that the PDLIM2 may be a promising target for the treatment of HCC.

Automated summary

Hepatocellular carcinoma (HCC) is a common and deadly malignancy worldwide. This study found that the downregulation of PDLIM2 in HCC is associated with poor prognosis, and overexpressed PDLIM2 can inhibit HCC cell proliferation, migration, invasion, and EMT by regulating beta-catenin, suggesting PDLIM2 as a promising therapeutic target for HCC.