CMV70-3P miRNA contributes to the CMV mediated glioma stemness and represents a target for glioma experimental therapy

// Ilya V. Ulasov 1, 2, 3 , Natalya V. Kaverina 3, 4 , Dhimankrishna Ghosh 1 , Marya A. Baryshnikova 2, 3 , Zaira G. Kadagidze 3 , Apollon I. Karseladze 3 , Anatoly Y. Baryshnikov 2, 3 , Charles S. Cobbs 1 1 Swedish Neuroscience Institute, Center for Advanced Brain Tumor Treatment, Seattle, WA, 98122, USA 2 Institute of Experimental Diagnostics and Therapy of Tumors, N.N. Blokhin Russian Cancer Research Center, Moscow, 115478, Russia 3 NN. Blokhin Cancer Research Center, RAMN, Moscow, 115478, Russia 4 Current employment: Division of Nephrology, University of Washington, Seattle, 98109, WA, USA Correspondence to: Ilya V. Ulasov, email: Ilya.Ulasov@Swedish.org Charles S. Cobbs, email: Charles.Cobbs@Swedish.org Keywords: brain tumor, cytomegalovirus, glioma stem cells, miRNA Received: November 17, 2015 Accepted: July 26, 2016 Published: August 10, 2016 ABSTRACT Glioblastoma multiforme (GBM) is a rapidly progressive brain tumor with a median survival of 15–19 months. Therapeutic resistance and recurrence of the disease is attributed to cancer stem cells (CSC). Here, we report that CMV70-3P miRNA encoded by CMV increases GBM CSC stemness. Inhibition of CMV70-3P expression using oligo inhibitors significantly attenuated the ability of primary glioma cells to proliferate and form neurospheres. At the molecular level, we show that CM70-3P increases expression of cellular SOX 2. Collectively, these findings indicate that CMV70-3P is a potential regulator of CMV- mediated glioma progression and cancer stemness.