| Literature DB >> 25117712 |
Liem H Nguyen1, Daisy A Robinton2, Marc T Seligson2, Linwei Wu3, Lin Li1, Dinesh Rakheja4, Sarah A Comerford5, Saleh Ramezani6, Xiankai Sun6, Monisha S Parikh1, Erin H Yang1, John T Powers2, Gen Shinoda2, Samar P Shah2, Robert E Hammer7, George Q Daley8, Hao Zhu9.
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.Entities:
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Year: 2014 PMID： 25117712 PMCID： PMC4145706 DOI： 10.1016/j.ccr.2014.06.018
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743