FAM188B promotes the growth, metastasis, and invasion of hepatocellular carcinoma by targeting the hnRNPA1/PKM2 axis

• Published in: Biochimica et biophysica acta. Molecular cell research Vol. 1871; no. 7; p. 119773
• Main Authors: Mu, Mingshan, Lu, Yisong, Tu, Kangsheng, Tu, Linglan, Guo, Chaoqin, Li, Zilin, Zhang, Xu, Chen, Yihong, Liu, Xin, Xu, Qiuran, Huang, Dongsheng, Li, Xiaoyan
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2024
• Subjects: Deubiquitinase; FAM188B; Hepatocellular carcinoma; hnRNPA1/PKM2 pathway; FAM188B; Hepatocellular carcinoma; hnRNPA1/PKM2 pathway; Deubiquitinase
• ISSN: 0167-4889; 1879-2596; 1879-2596
• DOI: 10.1016/j.bbamcr.2024.119773

Hepatocellular carcinoma (HCC), the leading cause of cancer-related deaths worldwide, is characterised by rapid growth and marked invasiveness. Accumulating evidence suggests that deubiquitinases play a pivotal role in HCC growth and metastasis. However, the expression of the deubiquitinase FAM188B and its biological functions in HCC remain unknown. The aim of our study was to investigate the potential role of FAM188B in HCC. The expression of FAM188B was significantly upregulated in liver cancer cells compared to normal liver cells, both at the transcriptional and translational levels. Similarly, FAM188B expression was higher in liver cancer tissues than in normal liver tissues. Bioinformatic analysis revealed that high FAM188B expression was associated with poor prognosis in patients with HCC. We further demonstrated that FAM188B knockdown inhibited cell proliferation, epithelial-mesenchymal transition, migration and invasion both in vitro and in vivo. Mechanistically, FAM188B knockdown significantly inhibited the hnRNPA1/PKM2 pathway in HCC cells. FAM188B may inhibit ubiquitin-mediated degradation of hnRNPA1 through deubiquitination. Notably, we observed that the inhibitory effects of FAM188B knockdown on HCC cell proliferation, migration and invasion were reversed when hnRNPA1 expression was restored. In conclusion, FAM188B promotes HCC progression by enhancing the deubiquitination of hnRNPA1 and subsequently activating the hnRNPA1/PKM2 pathway. Therefore, targeting FAM188B is a potential strategy for HCC therapy. •Deubiquitinating enzymes as targets of antitumor immunity in cancer immunotherapy•Heterogeneous nuclear ribonucleo proteins contributing to cancer progression•FAM188B, a key factor in the occurrence and development of hepatocellular carcinoma•FAM188B regulates the hnRNPA1–PKM2 signalling pathway