Oncotarget

Research Papers:

Non coding RNA analysis in fibrolamellar hepatocellular carcinoma

Benjamin A. Farber, Gadi Lalazar, Elana P. Simon, William J. Hammond, David Requena, Umesh K. Bhanot, Michael P. La and Sanford M. Simon _

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Oncotarget. 2018; 9:10211-10227. https://doi.org/10.18632/oncotarget.23325

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Abstract

Benjamin A. Farber1,2, Gadi Lalazar1, Elana P. Simon1, William J. Hammond1,2, David Requena1, Umesh K. Bhanot3, Michael P. La Quaglia2 and Sanford M. Simon1

1Laboratory of Cellular Biophysics, The Rockefeller University, New York, 10065 NY, USA

2Division of Pediatric Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, 10065 NY, USA

3Pathology Core Facility Memorial Sloan-Kettering Cancer Center, New York, 10065 NY, USA

Correspondence to:

Sanford M. Simon, email: simon@rockefeller.edu

Keywords: pediatric cancer; fusion protein; microRNA; lncRNAs; liver cancer

Received: September 11, 2017     Accepted: December 08, 2017     Published: December 15, 2017

ABSTRACT

Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver cancer found in adolescents and young adults without underlying liver disease. A deletion of ~400 kD has been found in one copy of chromosome 19 in the tumor tissue of all patients tested. This produces a fusion of the genes DNAJB1 and PRKACA which, in turn, produces a chimeric transcript and protein. Transcriptomic analysis of the tumor has shown upregulation of various oncologically relevant pathways, including EGF/ErbB, Aurora Kinase A, pak21 and wnt. To explore other factors that may contribute to oncogenesis, we examined the microRNA (miRNA) and long non-coding RNA (lncRNA) expression in FLC. The non-coding RNA expression profile in tumor tissue samples is distinctly different from the adjacent normal liver and from other liver tumors. Furthermore, miRZip knock down or over expression of certain miRNAs led to changes in the levels of coding genes that recapitulated changes observed in FLC, suggesting mechanistically that the changes in the cellular levels of miRNA are not merely correlative. Thus, in addition to serving as diagnostic tools for FLC, non-coding RNAs may serve as therapeutic targets.


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