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

被引：200

作者：

Nguyen, Liem H. ^{[1
,2
]}

Robinton, Daisy A. ^{[3
]}

Seligson, Marc T. ^{[3
]}

Wu, Linwei ^{[1
,2
,4
]}

Li, Lin ^{[1
,2
]}

Rakheja, Dinesh ^{[5
,6
,7
]}

Comerford, Sarah A. ^{[8
]}

Ramezani, Saleh ^{[9
,10
]}

Sun, Xiankai ^{[9
,10
]}

Parikh, Monisha S. ^{[1
,2
]}

Yang, Erin H. ^{[1
,2
]}

Powers, John T. ^{[3
]}

Shinoda, Gen ^{[3
]}

Shah, Samar P. ^{[3
]}

Hammer, Robert E. ^{[11
]}

Daley, George Q. ^{[3
]}

Zhu, Hao ^{[1
,2
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Childrens Res Inst, Dept Pediat, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Childrens Res Inst, Dept Internal Med, Dallas, TX 75390 USA

[3] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Div Pediat Hematol Oncol,Childrens Hosp Boston, Boston, MA 02115 USA

[4] Sun Yat Sen Univ, Affiliated Hosp 1, Organ Transplant Ctr, Guangzhou 510080, Guangdong, Peoples R China

[5] Childrens Med Ctr, Dept Pathol, Dallas, TX 75390 USA

[6] Childrens Med Ctr, Dept Pediat, Dallas, TX 75390 USA

[7] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

[8] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA

[9] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA

[10] Univ Texas SW Med Ctr Dallas, Adv Imaging Res Ctr, Dallas, TX 75390 USA

[11] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

来源：

CANCER CELL | 2014年 / 26卷 / 02期

关键词：

PREDICTS EARLY RECURRENCE; MESSENGER-RNA; PROMOTES TRANSFORMATION; POOR-PROGNOSIS; LIN-28; HOMOLOG; EXPRESSION; GROWTH; MYC; LET-7; IDENTIFICATION;

D O I：

10.1016/j.ccr.2014.06.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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.

引用

页码：248 / 261

页数：14

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