PRAJA is overexpressed in glioblastoma and contributes to neural precursor development

Joshua Shin1, Viveka Mishra2, Eric Glasgow3, Sobia Zaidi4, Kazufumi Ohshiro4, Bhargava Chitti5, Jian Chen9, Amee A. Kapadia6, Neha Rana7, Lopa Mishra4, Chu-Xia Deng8, Shuyun Rao4 and Bibhuti Mishra4

1 University of Virginia, Charlottesville, VA, USA

2 Massachusetts Institute of Technology, Cambridge, MA, USA

3 Department of Molecular Oncology, Georgetown University, Washington, DC, USA

4 Center for Translational Medicine, Department of Surgery, George Washington University, Washington, DC, USA

5 Department of Medicine, George Washington University, Washington, DC, USA

6 John Hopkins University, Department of Chemical and Biomolecular Engineering, Baltimore, MD, USA

7 McLean High School, McLean, VA, USA

8 Faculty of Health Sciences, University of Macau, Macau SAR, China

9 Department of Gastroenterology, Hepatology, & Nutrition, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA

Correspondence:

Bibhuti Mishra, email:

Correspondence:

Shuyun Rao, email:

Keywords: PRAJA, glioblastoma, apoptosis

Received: September 02, 2017 Accepted: September 08, 2017 Published: September 21, 2017

This article has been corrected. Genes&Cancer. 2017;8:745. https://doi.org/10.18632/genesandcancer.158

Abstract

PRAJA, a RING-H2 E3 ligase, is abundantly expressed in brain tissues such as the cerebellum and frontal cortex, amongst others, and more specifically in neural progenitor cells as well as in multiple cancers that include glioblastomas. However, the specific role that Praja plays in neural development and gliomas remains unclear. In this investigation, we performed bioinformatic analyses to examine Praja1 and Praja2 expression across 29 cancer types, and observed raised levels of Praja1 and Praja2 in gliomas with an inverse relationship between Praja1 and apoptotic genes and Praja substrates such as Smad3. We analyzed the role of Praja in the developing brain through loss of function studies, using morpholinos targeting Praja1 in embryonic zebrafish, and observed that Praja1 is expressed prominently in regions enriched with neural precursor cell subtypes. Antisense Praja morpholinos resulted in multiple embryonic defects including delayed neural development likely through increased apoptosis. Further studies revealed high levels of Cdk1 with loss of Praja1 in TGF-β or insulin treated cells, supporting the link between Praja1 and cell cycle regulation. In summary, these studies underscore Praja’s role in mammalian brain development and Praja1 deregulation may lead to gliomas possibly through the regulation of cell cycle and/or apoptosis.