转移
癌症研究
癌变
肝细胞癌
河马信号通路
生物
原癌基因酪氨酸蛋白激酶Src
信号转导
癌症
长非编码RNA
下调和上调
转录因子
表型
基因
细胞生物学
遗传学
作者
Xianghuo He,Jinggui Chen,Jiamin Zhou,Anrong Mao,Weiqi Xu,Hongxu Zhu,Qi Pan,Yiming Zhao,Ning Zhang,Lu Wang,Miao Wang,Zeyang Liu,Wei-Ping Zhu,Lu Wang
标识
DOI:10.1096/fj.202200825r
摘要
Regardless of the improvements in diagnostic and therapeutic methods, the clinical outcomes of hepatocellular carcinoma (HCC) patients remain poor. Although accumulating evidence indicates that lncRNAs (long noncoding RNAs) are essential within the control of tumorigenesis and the metastasis of cancer, the underlying mechanisms remain largely unknown. This work explored the pattern of expression and functional significance of a newly found lncRNA, Ewing sarcoma-associated transcript 1 (EWSAT1), in HCC metastasis. The results indicated that EWSAT1 was upregulated significantly in HCC relative to that in normal tissues and was correlated with an aggressive phenotype and low patient survival. Functional experiments demonstrated that EWSAT1 could promote proliferation and HCC cell metastasis both in vitro and in vivo. Mechanistically, EWSAT1 binds directly to Yes-associated protein (YAP), promotes Sarcoma gene (Src)-induced phosphorylation of YAP, facilitates nuclear translocation of YAP, and consequently, activates the transcription of Hippo-YAP signaling target genes involved in cancer evolution. This study found that EWSAT1 plays a crucial role in HCC metastasis and that it has the potential to be a prognosis biomarker and a target for therapeutics.
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