Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models

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

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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.

Original languageEnglish (US)
Pages (from-to)248-261
Number of pages14
JournalCancer Cell
Volume26
Issue number2
DOIs
StatePublished - Aug 11 2014

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ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Nguyen, L. H., Robinton, D. A., Seligson, M. T., Wu, L., Li, L., Rakheja, D., Comerford, S. A., Ramezani, S., Sun, X., Parikh, M. S., Yang, E. H., Powers, J. T., Shinoda, G., Shah, S. P., Hammer, R. E., Daley, G. Q., & Zhu, H. (2014). Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models. Cancer Cell, 26(2), 248-261. https://doi.org/10.1016/j.ccr.2014.06.018