RNA结合蛋白NELFE的致癌激活与肝细胞癌中的MYC信号传导
Oncogenic Activation of the RNA Binding Protein NELFE and MYC Signaling in Hepatocellular Carcinoma.
作者信息
Dang Hien, Takai Atsushi, Forgues Marshonna, Pomyen Yotsowat, Mou Haiwei, Xue Wen, Ray Debashish, Ha Kevin C H, Morris Quaid D, Hughes Timothy R, Wang Xin Wei
机构信息
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
出版信息
Cancer Cell. 2017 Jul 10;32(1):101-114.e8. doi: 10.1016/j.ccell.2017.06.002.
Abstract
Global transcriptomic imbalance is a ubiquitous feature associated with cancer, including hepatocellular carcinoma (HCC). Analyses of 1,225 clinical HCC samples revealed that a large numbers of RNA binding proteins (RBPs) are dysregulated and that RBP dysregulation is associated with poor prognosis. We further identified that oncogenic activation of a top candidate RBP, negative elongation factor E (NELFE), via somatic copy-number alterations enhanced MYC signaling and promoted HCC progression. Interestingly, NELFE induces a unique tumor transcriptome by selectively regulating MYC-associated genes. Thus, our results revealed NELFE as an oncogenic protein that may contribute to transcriptome imbalance in HCC through the regulation of MYC signaling.
摘要
全球转录组失衡是包括肝细胞癌（HCC）在内的癌症普遍存在的特征。对1225份临床HCC样本的分析表明，大量RNA结合蛋白（RBP）失调，且RBP失调与预后不良相关。我们进一步发现，通过体细胞拷贝数改变，顶级候选RBP负延长因子E（NELFE）的致癌激活增强了MYC信号传导并促进了HCC进展。有趣的是，NELFE通过选择性调节与MYC相关的基因诱导独特的肿瘤转录组。因此，我们的结果表明NELFE是一种致癌蛋白，可能通过调节MYC信号传导导致HCC转录组失衡。
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