肝细胞癌
基因沉默
泛素
癌症研究
转移
化学
细胞生物学
生物
癌症
遗传学
生物化学
基因
作者
Xingliu Hu,Guanrong Chen,Yuancheng Huang,Q Chen,Jianyong Zhuo,Renyi Su,Chiyu He,Yichao Wu,Zhikun Liu,Beng Yang,S. Wang,Liang Meng,Shuier Zheng,Di Lu,Qiang Wei,Jiaying Yang,Xuyong Wei,Ronggao Chen,Xiao Xu
标识
DOI:10.1002/advs.202306915
摘要
Abstract Recent studies suggest that circular RNA (circRNA)‐mediated post‐translational modification of RNA‐binding proteins (RBP) plays a pivotal role in metastasis of hepatocellular carcinoma (HCC). However, the specific mechanism and potential clinical therapeutic significance remain vague. This study attempts to profile the regulatory networks of circRNA and RBP using a multi‐omics approach. Has_circ_0006646 (circ0006646) is an unreported circRNA in HCC and is associated with a poor prognosis. Silencing of circ0006646 significantly hinders metastasis in vivo. Mechanistically, circ0006646 prevents the interaction between nucleolin (NCL) and the E3 ligase tripartite motif‐containing 21 to reduce the proteasome‐mediated degradation of NCL via K48‐linked polyubiquitylation. Furthermore, the change of NCL expression is proven to affect the phosphorylation levels of multiple proteins and inhibit p53 translation. Moreover, patient‐derived tumor xenograft and lentivirus injection, which is conducted to simulate clinical treatment confirmed the potential therapeutic value. Overall, this study describes the integrated multi‐omics landscape of circRNA‐mediated NCL ubiquitination degradation in HCC metastasis and provides a novel therapeutic target.
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