RNA over-editing of BLCAP contributes to hepatocarcinogenesis identified by whole-genome and transcriptome sequencing
RNA over-editing of BLCAP contributes to hepatocarcinogenesis identified by whole-genome and transcriptome sequencing
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全基因组和转录组测序发现，BLCAP 的 RNA 过度编辑导致肝癌发生
DOI：
10.1016/j.canlet.2014.12.006
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发表时间：
2015-02-28
期刊：
影响因子：
9.7
通讯作者：
Huang, Jian
中科院分区：
文献类型：
--
作者：
Hu, Xueda;Wan, Shengqing;Huang, Jian
肝细胞癌（HCC）是世界范围内最常见的癌症之一，尽管近几十年来这种疾病的治疗方法几乎没有变化，因为大多数引发这种疾病的遗传事件仍然未知。为了在分子水平上更好地了解HCC的发病机制并揭示新的肿瘤启动事件，我们整合了来自两对HCC组织的RNA-seq和DNA-seq数据。我们发现BLCAP在HCC中是一种新的编辑基因，与邻近肝组织相比，在40.1%的HCC中有过编辑表达。然后，我们使用RNA干扰和基因转染来评估BLCAP RNA编辑在肿瘤增殖中的作用。我们的研究结果表明，与野生型BLCAP基因相比，rna编辑的BLCAP基因可以通过增强AICT、mTOR和MDM2的磷酸化以及抑制TP53的磷酸化，稳定地促进细胞增殖（包括细胞生长、体外集落形成和体内致瘤性）。我们目前的研究结果表明，BLCAP基因的RNA过度编辑可能通过激活AKT/mTOR信号通路，成为晚期HCC的一种新的潜在驱动因素。2014爱思唯尔爱尔兰有限公司版权所有。
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, although the treatment of this disease has changed little in recent decades because most of the genetic events that initiate this disease remain unknown. To better understand HCC pathogenesis at the molecular level and to uncover novel tumor-initiating events, we integrated RNA-seq and DNA-seq data derived from two pairs of HCC tissues. We found that BLCAP is novel editing gene in HCC and has over-editing expression in 40.1% HCCs compared to adjacent liver tissues. We then used RNA interference and gene transfection to assess the roles of BLCAP RNA editing in tumor proliferation. Our results showed that compared to the wild-type BLCAP gene, the RNA-edited BLCAP gene may stably promote cell proliferation (including cell growth, colony formation in vitro, and tumorigenicity in vivo) by enhancing the phosphorylation of AICT, mTOR, and MDM2 and inhibiting the phosphorylation of TP53. Our current results suggest that the RNA over-editing of BLCAP gene may serve as a novel potential driver in advanced HCC through activating AKT/mTOR signal pathway. (C) 2014 Elsevier Ireland Ltd. All rights reserved.