Lin28b 足以驱动肝癌，并在小鼠模型中维持其生长。
Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models.
机构信息
Children's Research Institute, Departments of Pediatrics and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Division of Pediatric Hematology/Oncology, Children's Hospital Boston, Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
出版信息
Cancer Cell. 2014 Aug 11;26(2):248-61. doi: 10.1016/j.ccr.2014.06.018.
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.
Lin28a/b 是 RNA 结合蛋白，可影响干细胞的维持、代谢和致癌作用。分化不良、侵袭性强的癌症常过度表达 Lin28，但它在肿瘤起始或维持中的作用尚未得到明确解决。我们报告称，LIN28B 的过表达足以在小鼠模型中引发肝母细胞瘤和肝细胞癌。我们还在 MYC 驱动的肝母细胞瘤中检测到 Lin28b 的过表达，而 Lin28a/b 的肝特异性缺失则减少了肿瘤负担、延长了潜伏期并延长了生存期。针对 Lin28b 的静脉内 siRNA 和条件性 Lin28b 缺失均减少了肿瘤负担并延长了生存期。Igf2bp 蛋白上调，并且在 LIN28B 过表达的情况下，Igf2bp3 是必需的，以促进生长。因此，多种小鼠模型表明 Lin28b 既足以引发肝癌，也需要其维持。
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