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

Cancer Gene Therapy volume 28, pages 1113–1124 (2021)Cite this article

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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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Fig. 1: PDLIM2 is downregulated in HCC tissues and cells.
Fig. 2: PDLIM2 suppresses the proliferation and growth of HCC cells both in vitro and in vivo.
Fig. 3: PDLIM2 suppresses migration, invasion, and metastasis of hepatocellular carcinoma (HCC) cells.
Fig. 4: PDLIM2 is mainly localized in the cytoplasm of HCC cells.
Fig. 5: PDLIM2 suppresses β-catenin activity and downstream gene expression.
Fig. 6: PDLIM2 suppresses EMT in HCC cells and lung metastasis by regulating β-catenin.
Fig. 7: Role of PDLIM2 in the development and epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) by regulating β-catenin.

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Acknowledgements

We acknowledge and appreciate our colleagues for their valuable suggestions and technical assistance for this study.

Funding

This study was supported by the National Natural Science Foundation of China (81800557), and China Postdoctoral Science Foundation (2018M631886).

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Author notes

  1. These authors contributed equally: Xiaoming Jiang, Zhe Chu

Authors and Affiliations

  1. Clinical Laboratory, the First Hospital of Jilin University, Changchun, 130000, China

    Xiaoming Jiang, Zhe Chu, Yang Cao & Xu Shi

  2. Department of Emergency, the First Hospital of Jilin University, Changchun, 130000, China

    Xiaoming Jiang & Zhe Chu

  3. Department of Respiration, the First Hospital of Jilin University, Changchun, 130000, China

    Ying Tang

  4. Department of Hepatology, Medical School of Jilin University, Changchun, 130000, China

    Ying Shi

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  1. Xiaoming Jiang
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Contributions

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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Correspondence to Ying Shi or Xu Shi.

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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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