Lin28b is Sufficient to Drive Liver Cancer and Necessary for Its Maintenance in Murine Models

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2014 Aug 14

PMID 25117712

Citations 121

Authors

Liem H Nguyen

Daisy A Robinton

Marc T Seligson

Linwei Wu

Lin Li

Dinesh Rakheja

Sarah A Comerford

Saleh Ramezani

Xiankai Sun

Monisha S Parikh

Erin H Yang

John T Powers

Gen Shinoda

Samar P Shah

Robert E Hammer

George Q Daley

Hao Zhu

Affiliations

Soon will be listed here.

Abstract

Lin28a/b are RNA-binding proteins that influence stem cell maintenance, metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often overexpress Lin28, but its role in tumor initiation or maintenance has not been definitively addressed. We report that LIN28B overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated, and Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Therefore, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance.

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