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

被引:1
|
作者
Mu, Mingshan [1 ]
Lu, Yisong [1 ]
Tu, Kangsheng [2 ]
Tu, Linglan [3 ]
Guo, Chaoqin [1 ]
Li, Zilin [1 ]
Zhang, Xu [1 ]
Chen, Yihong [1 ]
Liu, Xin [4 ]
Xu, Qiuran [1 ,4 ,5 ]
Huang, Dongsheng [4 ]
Li, Xiaoyan [1 ]
机构
[1] Sch Basic Med Sci & Forens Med, Hangzhou 310053, Zhejiang, Peoples R China
[2] Xi An Jiao Tong Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Xian 710061, Shaanxi, Peoples R China
[3] Hangzhou Med Coll, Sch Lab Med & Bioengn, Hangzhou 310053, Zhejiang, Peoples R China
[4] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Lab Tumor Mol Diag & Individualized Med Zhejiang P, Hangzhou 310014, Zhejiang, Peoples R China
[5] Hangzhou Med Coll, Zhejiang Prov Peoples Hosp, Affiliated Peoples Hosp, Zhejiang Key Lab Tumor Mol Diag & Individualized M, Hangzhou 310014, Zhejiang, Peoples R China
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2024年 / 1871卷 / 07期
关键词
Hepatocellular carcinoma; FAM188B; Deubiquitinase; hnRNPA1/PKM2; pathway; HNRNP A1; FAMILY;
D O I
10.1016/j.bbamcr.2024.119773
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:10
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