Gene Identified That Promotes Childhood Cancers

Ribonucleic acid (RNA)-binding proteins that influence stem cell maintenance, metabolism, and oncogenes, and in poorly differentiated, aggressive cancers are often overexpressed, have their role in tumor initiation or maintenance not definitively addressed.

Scientists at The University of Texas Southwestern Medical Center (Dallas, TX, USA) used a murine model to study the RNA-binding proteins Lin28a/b. The Lin-28 Homolog B gene (LIN28B) overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. The team also detected LIN28B overexpression in V-Myc Avian Myelocytomatosis Viral Oncogene Homolog (MYC)-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival.

Insulin-like growth factor 2 mRNA binding protein (Igf2bp) proteins are upregulated, and the gene Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Therefore, the multiple murine models demonstrate that LIN28B is both sufficient to initiate liver cancer and necessary for its maintenance. Both intravenous small interfering RNA (siRNA) against LIN28B and conditional LIN28B deletion reduced tumor burden and prolonged survival.

Hao Zhu, MD, a professor of Pediatrics and Internal Medicine and senior author of the study said. “We and others have found that LIN28B—a gene that is normally turned on in fetal but not adult tissues—is expressed in several childhood cancers, including neuroblastoma, Wilms' tumor, and hepatoblastoma, a type of cancer that accounts for nearly 80% of all liver tumors in children. In our study, we found that overproduction of LIN28B specifically causes hepatoblastoma, while blocking LIN28B impairs the cancer's growth. This opens up the possibility that pediatric liver cancer patients could one day be treated without resorting to chemotherapy.” The study was published on August 11, 2014, in the journal Cancer Cell.

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The University of Texas Southwestern Medical Center