Oncogenic Activation of the RNA Binding Protein NELFE and MYC Signaling in Hepatocellular Carcinoma

肝细胞癌中 RNA 结合蛋白 NELFE 和 MYC 信号的致癌激活

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作者:Hien Dang, Atsushi Takai, Marshonna Forgues, Yotsowat Pomyen, Haiwei Mou, Wen Xue, Debashish Ray, Kevin C H Ha, Quaid D Morris, Timothy R Hughes, Xin Wei Wang

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.

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