Abstract
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 β-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 β-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 β-catenin in HCC were investigated by using a nude mouse xenograft model. It should be noted that PDLIM2 led to the inhibition of β-catenin activity and its downstream gene expression. Importantly, ectopic PDLIM2 expression inhibited the proliferation, migration, invasion, and EMT of HCC cells by reducing β-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 β-catenin. This study suggests that the PDLIM2 may be a promising target for the treatment of HCC.
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Acknowledgements
We acknowledge and appreciate our colleagues for their valuable suggestions and technical assistance for this study.
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This study was supported by the National Natural Science Foundation of China (81800557), and China Postdoctoral Science Foundation (2018M631886).
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Xiaoming Jiang and Ying Tang designed the study. Zhe Chu was involved in data collection. Yang Cao and Ying Shi performed the statistical analysis and preparation of figures. Ying Tang and Xu Shi drafted the paper. All authors read and approved the final manuscript.
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Jiang, X., Chu, Z., Cao, Y. et al. PDLIM2 prevents the malignant phenotype of hepatocellular carcinoma cells by negatively regulating β-catenin. Cancer Gene Ther 28, 1113–1124 (2021). https://doi.org/10.1038/s41417-020-00257-6
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DOI: https://doi.org/10.1038/s41417-020-00257-6