Pseudogene RACGAP1P activates RACGAP1/Rho/ERK signalling axis as a competing endogenous RNA to promote hepatocellular carcinoma early recurrence
Pseudogene RACGAP1P activates RACGAP1/Rho/ERK signalling axis as a competing endogenous RNA to promote hepatocellular carcinoma early recurrence
复制标题
假基因RACGAP1P作为竞争性内源RNA激活RACGAP1/Rho/ERK信号轴促进肝细胞癌早期复发
DOI：
10.1038/s41419-019-1666-2
复制
发表时间：
2019-06-03
影响因子：
9
通讯作者：
Liu, Jin-Quan
中科院分区：
文献类型：
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作者：
Wang, Meng-Yao;Chen, Dong-Ping;Liu, Jin-Quan
越来越多的证据表明假基因在人类癌症中起着至关重要的作用。然而，假基因在HCC发病机制，特别是HCC早期复发中的作用尚未完全阐明。在此，我们发现了一种新的与早期复发相关的假基因RACGAP1P，该基因在HCC中显著上调，与肿瘤大小较大、临床分期较晚、AFP水平异常和生存时间较短相关。体外和体内实验表明，RACGAP1P是HCC细胞发生恶性特征的先决条件，包括细胞生长和迁移。机制研究表明，RACGAP1P作为一种ceRNA激发其致癌活性，将miR-15-5p从其内源性靶标RACGAP1中分离出来，从而导致RACGAP1上调，激活RhoA/ERK信号传导。这些结果可能为HCC早期复发过程中假基因/miRNA/亲本基因遗传网络的功能串扰提供新的见解，并可能有助于改善这类HCC患者的临床干预。
Accumulating evidence has indicated crucial roles for pseudogenes in human cancers. However, the roles played by pseudogenes in the pathogenesis of HCC, particularly HCC early recurrence, still incompletely elucidated. Herein, we identify a novel early recurrence related pseudogene RACGAP1P which was significantly upregulated in HCC and was associated with larger tumour size, advanced clinical stage, abnormal AFP level and shorter survival time. In vitro and in vivo experiments have shown that RACGAP1P is a prerequisite for the development of malignant characteristics of HCC cells, including cell growth and migration. Mechanistic investigations indicated that RACGAP1P elicits its oncogenic activity as a ceRNA to sequestrate miR-15-5p from its endogenous target RACGAP1, thereby leading to the upregulation of RACGAP1 and the activation of RhoA/ERK signalling. These results may provide new insights into the functional crosstalk of the pseudogene/miRNA/parent-gene genetic network during HCC early relapse and may contribute to improving the clinical intervention for this subset of HCC patients.