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Cancer Cell. 2017 Jul 10;32(1):101-114.e8. doi: 10.1016/j.ccell.2017.06.002.

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

Author information

1
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
2
RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA.
3
RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester, MA 01605, USA; Program in Molecular Medicine, Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
4
Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
5
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1, Canada.
6
Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5S 3E1, Canada.
7
Donnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 3E1, Canada.
8
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: xw3u@nih.gov.

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.

KEYWORDS:

MYC; NELFE; RDBP; RNA binding proteins; cancer; hepatocellular carcinoma; oncogene; transcriptome

PMID:
28697339
PMCID:
PMC5539779
DOI:
10.1016/j.ccell.2017.06.002
[Indexed for MEDLINE]
Free PMC Article

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