NDLI: Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) is an important protumorigenic factor in hepatocellular carcinoma.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Gutschner, Tony Hämmerle, Monika Pazaitis, Nikolaos Bley, Nadine Fiskin, Evgenij Uckelmann, Hannah Heim, Andreas Groß, Matthias Hofmann, Nina Geffers, Robert Skawran, Britta Longerich, Thomas Breuhahn, Kai Schirmacher, Peter Mühleck, Britta Hüttelmaier, Stefan Diederichs, Sven
Description	Country affiliation: Germany Author Affiliation: Gutschner T ( Helmholtz-University-Group 'Molecular RNA Biology & Cancer,' German Cancer Research Center DKFZ & Institute of Pathology, University Hospital Heidelberg, Germany.)
Abstract	UNLABELLED: Hepatocarcinogenesis is a stepwise process. It involves several genetic and epigenetic alterations, e.g., loss of tumor suppressor gene expression (TP53, PTEN, RB) as well as activation of oncogenes (c-MYC, MET, BRAF, RAS). However, the role of RNA-binding proteins (RBPs), which regulate tumor suppressor and oncogene expression at the posttranscriptional level, are not well understood in hepatocellular carcinoma (HCC). Here we analyzed RBPs induced in human liver cancer, revealing 116 RBPs with a significant and more than 2-fold higher expression in HCC compared to normal liver tissue. We focused our subsequent analyses on the Insulin-like growth factor 2 messenger RNA (mRNA)-binding protein 1 (IGF2BP1) representing the most strongly up-regulated RBP in HCC in our cohort. Depletion of IGF2BP1 from multiple liver cancer cell lines inhibits proliferation and induces apoptosis in vitro. Accordingly, murine xenograft assays after stable depletion of IGF2BP1 reveal that tumor growth, but not tumor initiation, strongly depends on IGF2BP1 in vivo. At the molecular level, IGF2BP1 binds to and stabilizes the c-MYC and MKI67 mRNAs and increases c-Myc and Ki-67 protein expression, two potent regulators of cell proliferation and apoptosis. These substrates likely mediate the impact of IGF2BP1 in human liver cancer, but certainly additional target genes contribute to its function. CONCLUSION: The RNA-binding protein IGF2BP1 is an important protumorigenic factor in liver carcinogenesis. Hence, therapeutic targeting of IGF2BP1 may offer options for intervention in human HCC.
File Format	HTM / HTML
ISSN	02709139
Issue Number	5
Volume Number	59
e-ISSN	15273350
Journal	Hepatology
Language	English
Publisher	Wiley
Publisher Date	2014-05-01
Publisher Place	United States
Access Restriction	Subscribed
Subject Keyword	Discipline Hepatology Carcinoma, Hepatocellular Etiology Liver Neoplasms Rna-binding Proteins Physiology Apoptosis Pathology Cell Proliferation Gene Expression Regulation, Neoplastic Hep G2 Cells Humans Ki-67 Antigen Genetics Proto-oncogene Proteins C-myc Journal Article Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Hepatology

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