细胞骨架
癌症研究
转移
生物
肌动蛋白细胞骨架
细胞生物学
肿瘤进展
多嘧啶结合蛋白
异相核糖核蛋白颗粒
调节器
肝细胞癌
RNA剪接
核糖核酸
癌症
生物化学
细胞
遗传学
基因
作者
Boqiang Liu,Hao Shen,Jing He,Binghan Jin,Yuanshi Tian,Weiqi Li,Lidan Hou,Weijun Zhao,Junjie Nan,Jia Zhao,Jiliang Shen,Hong Yu,Yifan Wang,Ge Shan,Liang Shi,Xiujun Cai
标识
DOI:10.1073/pnas.2220296120
摘要
Metastasis, especially intrahepatic, is a major challenge for hepatocellular carcinoma (HCC) treatment. Cytoskeleton remodeling has been identified as a vital process mediating intrahepatic spreading. Previously, we reported that HCC tumor adhesion and invasion were modulated by circular RNA (circRNA), which has emerged as an important regulator of various cellular processes and has been implicated in cancer progression. Here, we uncovered a nuclear circRNA, circASH2, which is preferentially lost in HCC tissues and inhibits HCC metastasis by altering tumor cytoskeleton structure. Tropomyosin 4 (TPM4), a critical binding protein of actin, turned out to be the major target of circASH2 and was posttranscriptionally suppressed. Such regulation is based on messenger RNA (mRNA)/precursormRNA splicing and degradation process. Furthermore, liquid–liquid phase separation of nuclear Y-box binding protein 1 (YBX1) enhanced by circASH2 augments TPM4 transcripts decay. Together, our data have revealed a tumor-suppressive circRNA and, more importantly, uncovered a fine regulation mechanism for HCC progression.
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