The Role of miR-7 in Neuronal Differentiation

Student: Ksenia Klue (College of Wooster) and Mihaela Paula Suciu (George Mason University)
Mentor: Surendra Ambegaokar (Department of Botany-Microbiology, Neuroscience Program)

The gene microRNA-7 is thought to have a role in brain development and several disorders including Alzheimer's disease, the sixth-leading cause of death in the United States. Studying how levels of microRNA-7 expression changes in brain cells as they grow and mature will allow better understanding of how microRNA-7 functions in healthy neurons, and what might be going wrong in diseases. Such knowledge could contribute to new therapies for Alzheimer’s disease, improving the lives of many.

MicroRNAs (miRNAs) are negative regulators of gene expression. Previous research has found microRNA-7 (miR-7) expression may be altered in neurobehavioral disorders, such as schizophrenia or Alzheimer’s disease; however research is inconclusive as to its role. Previous data have also found expression in developing brains of animals, but there are uncertainties as to whether miR-7 promotes or inhibits neuronal differentiation, or if miR-7 expression has any effect at all on neuronal differentiation. Our research uses SH-SY5Y cells, which are human glioblastoma cells that have neuronal progenitor-like properties, in that they can be induced to differentiate into neuron-like cells when treated with retinoic acid (RA). We examined if miR-7 expression changes during the course of differentiation. We also examined if overexpressing miR-7 was sufficient to induce neuronal differentiation, as measured by morphology and expression of neuronal-specific genes. We found miR-7 expression goes down during differentiation. In support of this, miR-7 overexpression was not sufficient to induce differentiation; however expression of some neuronal markers increased, which suggests miR-7 may have a partial and more complex role in differentiation. This research will better inform our understanding of microRNA function, and the potential use of miRNAs as therapeutic targets in neurobehavioral disorders.