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

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

doi:10.1016/j.ccell.2017.06.002

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

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

Authors

Affiliations

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.

Published by Elsevier Inc.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

MeSH terms

Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism
Cell Transformation, Neoplastic
Gene Expression Regulation, Neoplastic
Humans
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Proto-Oncogene Proteins c-myc / metabolism*
Signal Transduction
Transcription Factors / genetics
Transcription Factors / metabolism
Transcription Factors / physiology*

Substances

Proto-Oncogene Proteins c-myc
Transcription Factors
negative elongation factor

Abstract

Publication types

MeSH terms

Substances

Grants and funding