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

Mu, Mingshan; Lu, Yisong; Tu, Kangsheng; Tu, Linglan; Guo, Chaoqin; Li, Zilin; Zhang, Xu; Chen, Yihong; Liu, Xin; Xu, Qiuran; Huang, Dongsheng; Li, Xiaoyan

Mu, Mingshan; Lu, Yisong; Tu, Kangsheng; Tu, Linglan; Guo, Chaoqin; Li, Zilin; Zhang, Xu; Chen, Yihong; Liu, Xin; Xu, Qiuran; Huang, Dongsheng; Li, Xiaoyan.

Afiliación

Mu M; School of Basic Medical Sciences and Forensic Medicine, Hangzhou 310053, Zhejiang, China.
Lu Y; School of Basic Medical Sciences and Forensic Medicine, Hangzhou 310053, Zhejiang, China.
Tu K; Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Tu L; School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou 310053, Zhejiang, China.
Guo C; School of Basic Medical Sciences and Forensic Medicine, Hangzhou 310053, Zhejiang, China.
Li Z; School of Basic Medical Sciences and Forensic Medicine, Hangzhou 310053, Zhejiang, China.
Zhang X; School of Basic Medical Sciences and Forensic Medicine, Hangzhou 310053, Zhejiang, China.
Chen Y; School of Basic Medical Sciences and Forensic Medicine, Hangzhou 310053, Zhejiang, China.
Liu X; Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.
Xu Q; School of Basic Medical Sciences and Forensic Medicine, Hangzhou 310053, Zhejiang, China; Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejian
Huang D; Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China. Electronic address: dshuang@hmc.edu.cn.
Li X; School of Basic Medical Sciences and Forensic Medicine, Hangzhou 310053, Zhejiang, China; Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejian

Biochim Biophys Acta Mol Cell Res ; 1871(7): 119773, 2024 Oct.

Article en En | MEDLINE | ID: mdl-38844182

ABSTRACT

ABSTRACT

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.

Asunto(s)

Carcinoma Hepatocelular; Proteínas Portadoras; Proliferación Celular; Regulación Neoplásica de la Expresión Génica; Ribonucleoproteína Nuclear Heterogénea A1; Neoplasias Hepáticas; Proteínas de la Membrana; Invasividad Neoplásica; Humanos; Carcinoma Hepatocelular/patología; Carcinoma Hepatocelular/genética; Carcinoma Hepatocelular/metabolismo; Neoplasias Hepáticas/patología; Neoplasias Hepáticas/genética; Neoplasias Hepáticas/metabolismo; Ribonucleoproteína Nuclear Heterogénea A1/metabolismo; Ribonucleoproteína Nuclear Heterogénea A1/genética; Proliferación Celular/genética; Proteínas de la Membrana/genética; Proteínas de la Membrana/metabolismo; Proteínas Portadoras/metabolismo; Proteínas Portadoras/genética; Ratones; Animales; Línea Celular Tumoral; Movimiento Celular/genética; Ratones Desnudos; Transición Epitelial-Mesenquimal/genética; Masculino; Ratones Endogámicos BALB C; Metástasis de la Neoplasia; Femenino

Palabras clave

Deubiquitinase; FAM188B; Hepatocellular carcinoma; hnRNPA1/PKM2 pathway

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Portadoras / Regulación Neoplásica de la Expresión Génica / Carcinoma Hepatocelular / Proliferación Celular / Ribonucleoproteína Nuclear Heterogénea A1 / Neoplasias Hepáticas / Proteínas de la Membrana / Invasividad Neoplásica Límite: Animals / Female / Humans / Male Idioma: En Revista: Biochim Biophys Acta Mol Cell Res Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos

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