MicroRNA-10b-mediated Transformation of Neural Stem Cells to Glioblastoma Stem Cells

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Nadiya M. Teplyuk, PhD
Glioblastoma (GBM, or glioma of grade IV) is one of the most common and aggressive brain cancers with poor survival rates even with intensive treatment. Increasing evidence suggests that GBMs derive from glioma initiating cells (so-called cancer stem cells), which originate directly from neural stem cells in the process of malignant transformation. Therefore, targeting GBM initiating cells is important for reducing GBM growth. However, molecular events that lead to the transformation of normal neural progenitors to GBM-initiating stem cells are poorly understood.

Recent discovery of microRNAs, small regulatory RNA molecules, revolutionized the field of cancer biology. Since a single microRNA may control expression of multiple cellular proteins, de-regulation of one or a few microRNAs may lead to aberrant intracellular metabolism and cancer growth. Dr. Teplyuk and her team’s work over the past few years focused on the discovery of microRNAs that contribute to glioma initiation and progression, gathering mounting evidence indicating that microRNAs are essential regulators of GBM growth. The team has recently identified a specific microRNA, miR-10b, not expressed in normal brain cells, including neural stem cells. This same molecule is abundant in tumorigenic glioma-initiating stem cells, suggesting that miR-10b activation is an early event in the origin of a glioma. We found that miR-10b drives glioma cell division and may function as a molecule that promotes GBMs.

This project hypothesizes that induced expression of miR-10b in neural stem cells can cause malignant transformation. As miR-10b is highly specific target for GBM, we anticipate this work will set a background for development of a new therapeuties to use against GBMs.