The potential oncogenic role of the RAS-like GTP-binding gene RIT1 in glioblastoma

Article type: Research Article

Authors: Khalil, Athar^{a; *} | Nemer, Georges^{a; b; *}

Affiliations: [a] Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon | [b] Division of Genomics and Translational Biomedicine, College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar

Correspondence: [*] Corresponding authors: Athar Khalil, Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. E-mail: [email protected],DivisionofGenomicsandTranslationalBiomedicine,CollegeofHealthandLifeSciences,HamadBinKhalifaUniversity,Doha,Qatar.E-mails:[email protected]@hbku.edu.qa.

Abstract: Glioblastoma is the most common type of malignant brain tumors and the most feared cancer among adults. The poor prognosis among patients affected with this type of cancer is associated with its high-invasiveness and the lack of successful therapies. A comprehensive understanding for the early molecular mechanisms in glioblastoma would definitely enhance the diagnosis and the treatment strategies. Deregulated expression of key genes that are known to be involved in early neurogenesis could be the instigator of brain tumorigenesis. Ras Like Without CAAX 1 (RIT1) gene that encodes an unusual “orphan” GTPase protein belongs to this category of critical genes that are known to be involved in controlling sequential proliferation and differentiation of adult hippocampal neural progenitor cells. In this study, we surveyed RIT1 gene expression by in-silico approaches to determine its spatio-temporal pattern in glioblastoma. Our results revealed a significant and progressive upregulation of RIT1 mRNA levels in various publicly available datasets. RIT1 expression ranked among the top upregulated genes in glioblastoma cohorts and it correlated with poor overall survival. Genetic and epigenetic analysis of RIT1 didn’t reveal any significant aberration that could underlie its deregulated expression. Yet, our results highlighted the possibility of its activity to be transcriptionally controlled by STAT3, one of the main players in the onset of glioblastoma. In conclusion, our study presented for the first time a potential oncogenic role for RIT1 in glioblastoma. Knowing that the RAS superfamily of proteins has created an evolution in the cancer field, RIT1 should be added to this list through further investigations on its possible usage as a biomarker and therapeutic target in glioblastoma.

Keywords: RIT1, glioblastoma, bioinformatics, STAT3, clinical data

DOI: 10.3233/CBM-191264

Journal: Cancer Biomarkers, vol. 29, no. 4, pp. 509-519, 2020