Targeting RNA helicase DDX3 in stem cell maintenance and teratoma formation
Candace L. Kerr1, Guus M. Bol2,3 Farhad Vesuna2 and Venu Raman2,4,5
1 Department of Gynecology and Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
2 Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
3 Department of Oncology, University Medical Center Utrecht Cancer Center, GA Utrecht, The Netherlands
4 Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
5 Department of Pathology, University Medical Center Utrecht Cancer Center, GA Utrecht, The Netherlands
Correspondence:
Venu Raman, email:
Keywords: DDX3; stem cells; differentiation; RK-33; teratoma
Received: November 21, 2018 Accepted: January 13, 2019 Published: January 25, 2019
Abstract
DDX3 is an RNA helicase that has antiapoptotic properties, and promotes proliferation and transformation. Besides the role of DDX3 in transformed cells, there is evidence to indicate that DDX3 expression is at its highest levels during early embryonic development and is also expressed in germ cells of adults. Even though there is a distinct pattern of DDX3 expression during embryonic development and in adults, very little is known regarding its role in embryonic stem cells and pluripotency. In this work, we examined the relationship between DDX3 and human embryonic stem cells and its differentiated lineages. DDX3 expression was analyzed by immunohistochemistry in human embryonic stem cells and embryonal carcinoma cells. From the data obtained, it was evident that DDX3 was overexpressed in undifferentiated stem cells compared to differentiated cells. Moreover, when DDX3 expression was abrogated in multiple stem cells, proliferation was decreased, but differentiation was facilitated. Importantly, this resulted in reduced potency to induce teratoma formation. Taken together, these findings indicate a distinct role for DDX3 in stem cell maintenance.
