Borealin Promotes Tumor Growth and Metastasis by Activating the Wnt/β-Catenin Signaling Pathway in Hepatocellular Carcinoma

J Hepatocell Carcinoma. 2022 Mar 11:9:171-188. doi: 10.2147/JHC.S336452. eCollection 2022.

Abstract

Background and aims: Hepatocellular carcinoma (HCC) is a common malignant disease with high morbidity and mortality throughout the world. While Borealin is a putative oncogene that is dysregulated in multiple tumors, its exact role in HCC remains less investigated.

Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) assays were employed to examine the relative amount of Borealin. Gene set enrichment analysis (GSEA) and other bioinformatic analyses were implemented to probe into the potential functions of Borealin. The biological roles and mechanisms of Borealin in the tumorigenesis and development of HCC were further evaluated using a battery of functional assays in vivo and in vitro.

Results: Borealin was enhanced in the HCC tissue samples and hepatoma cells when compared with the nontumor tissues and normal liver cells. Higher Borealin expression was positively linked with advanced pathological phenotypes and inferior overall survival. The overexpression of Borealin promoted the cells' abilities on proliferation, invasion and epithelial-mesenchymal transition (EMT) in vitro, facilitated tumor growth and lung metastasis in vivo, whereas the silencing of Borealin inhibited these capabilities in vitro. Furthermore, Borealin interacted with β-catenin and further activated the Wnt/β-catenin signaling pathway, which endowed HCC cells with highly aggressive and metastatic capabilities.

Conclusion: Borealin was identified as an oncogene that could promote HCC growth and metastasis by activating the WNT/β-catenin signaling pathway. These findings extended the understanding of Borealin in HCC tumorigenesis and development and highlighted the significance of Borealin in HCC diagnosis and treatment.

Keywords: Borealin; Wnt/β-catenin; epithelial mesenchymal transition; hepatocellular carcinoma.

Grants and funding

This study was supported by the key scientific research project of Xiangyang Central Hospital (Award number: 2021ZD02) and Xiangyang Scientific and Technological Project (Award number: 2021YL07).