A RNA binding protein that plays an important role in the process of cancer growth

Recently, a study on gene expression in leukemia cells shows that a kind of RNA binding protein plays an important in promoting the development of cancer in rats. The proteins are usually active in the fetal tissue in the adult body is closed, but it was re-activated in a number of cancer cells. This expression pattern makes it an attractive anti-cancer drug target, because blocking its activity is unlikely to cause serious side effects.

The new study, published in the March 14 of the "Journal of Clinical Investigation" magazine, with a focus on a particularly aggressive B-cell acute lymphoblastic leukemia (ALL) - in children and adolescents, the most common type of leukemia. From the University of California, Santa Cruz (UC Santa) and the University of California at Los Angeles (UCLA) scientists led by a research team found that an RNA-binding protein (referred to as IGF2BP3) in this group of patients with B-ALL cancer cells It is excessive.

In this paper, co-author, UC Santa Cruz molecular, cellular and developmental biology associate professor Jeremy Sanford said, "This protein --IFG2BP3, with many types of cancer and the prognosis is poor exciting about this study is that it goes beyond. We first demonstrated that abnormal expression of this protein is sufficient to induce disease."

Such studies have identified by RNA binding proteins directly regulate genes; many of the genes are shown to be associated with cancer oncogene. In particular, the improved protein has a full understanding of the gene (called MYC) expression, which in turn has a large number of the regulation of the expression of genes associated with cell proliferation.

Compared with other proteins involved in the regulation of gene activity, RNA binding proteins have not been well studied. When a gene is turned on or "expression" of an RNA copy of the DNA sequence of the gene is composed, then, this "messenger RNA" carry the genetic code is translated into a protein, the exercise of some of the cell function. Many factors are involved in the regulation of gene transcription into messenger RNA which and when transcribed, but the RNA binding protein interaction with messenger RNA itself to the post-transcriptional regulation of gene expression has occurred. Scientists are just beginning to uncover the gene expression of post-transcriptional regulation of complexity.

Sanford said the case IGF2BP3 B cell leukemia, RNA binding proteins overall effect is that by altering the expression of numerous genes, and promotes the proliferation of B cells.

Leukemia begins in the bone marrow hematopoietic stem cells; it will cause all the different types of mature blood cells. A wide variety of genetic changes will occur resulting in abnormal proliferation of white blood cells, side by side out of normal blood cells. Sanford at UCLA collaborators Dinesh Rao, is research involving chromosome mixed lineage leukemia (MLL) gene rearrangements in B-ALL cases, this type of leukemia accounts for 5% of B-ALL patients with poor prognosis increased risk of early recurrence after treatment.

In Rao's lab will determine one of these cases IGF2BP3 most deregulated gene, they began working with Sanford laboratory to find out which genes are directly regulated by the IGF2BP3. Sanford and Rao is a friend since college when, Rao know, Sanford laboratory is to use a small number of "capture RNA binds to a specific protein molecule," one of the laboratory technology. This technique is known as single nucleotide resolution crosslinking immunoprecipitation (iCLIP), so that Sanford laboratory capable of identifying hundreds of RNA transcripts in IGF2BP3 binding sites in both B-ALL cell lines. They also found that, IGF2BP3 enhance MYC and other oncogenes in hematopoietic stem cell expression.

By studying this effect in mice, the researchers found, IGF2BP3 overexpressed in bone marrow, can lead to the proliferation of hematopoietic stem cells and B cell progenitor cells, resulting in B-ALL MLL- rearranged some of the features.

Sanford said, "Understanding its mechanism of action, for the exploration of treatment of 'can interfere with the proteins' function in the disease'. There is an important possibility that RNA-based therapies can isolate the protein and prevents it from binding to RNA transcription. This will be one method among the gene expressions related to cancer cell proliferation."

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