Analysis of microRNA Determinants of Survival in Glioblastoma

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Anna Krichevsky, PhD

Glioblastoma (GBM) is the most common and aggressive type of brain malignancy in adults and also accounts for approximately 10% of pediatric central nervous system tumors. The average lifespan of GBM patients is less than one year even with therapeutic interventions and has only minimally improved over the past 25 years. Therefore, there is a critical need for new molecular targets, concepts, and approaches to treat this devastating disease.

The discovery of microRNAs, small regulatory molecules with a great potential to control gene expression, has revolutionized the field of cancer biology. It suggested an entirely new layer of gene regulation that might be involved in progression and maintenance of human cancer. A single microRNA can directly regulate multiple target genes, and thereby control expression of multiple proteins involved in diverse signaling pathways. Over the past seven years, Dr. Krichevsky and her team have focused on microRNAs involved in glioma initiation and progression, and today have mounting evidence indicating that GBM growth and invasiveness are closely regulated by microRNAs.

The team has identified and investigated three specific onco-microRNAs—miR-21, miR-10b, and miR-296—as potent regulators of glioma cell division, tumor resistance to death signals, and glioma-induced angiogenesis. These molecules drive GBM growth. More recently, they predicted several protective microRNAs that may slow-down tumor growth and thus significantly increase patients’ survival. This studies the effects of such molecules on glioma growth in cultured cells and animal models of human GBM. If successful, it may lead to the development of novel microRNA-based therapies for gliomas.