Transcriptome evaluation of glioma cells treated with hypusine

• Grant number: 19/25517-2
• Support type: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): August 01, 2020
• Effective date (End): April 30, 2021
• Field of knowledge: Biological Sciences - Biology
• Principal researcher: Augusto Ducati Luchessi
• Grantee: Leticia Tamborlin
• Supervisor abroad: Michael Mathews
• Home Institution: Instituto de Biociências (IB). Universidade Estadual Paulista (UNESP). Campus de Rio Claro. Rio Claro , SP, Brazil
• Research place: Rutgers The State University of New Jersey, Newark, United States
• Associated to the scholarship: 17/21914-1 - Functional characterization of the amino acid hypusine, BP.DR

Abstract

The amino acid hypusine was first identified in 1971 from bovine brain extract. Later, this amino acid was found in the liver, kidney, muscle, and blood of other mammals. Hypusine is formed from a post-translational modification that occurs at the eukaryotic translation initiation factor 5A (eIF5A) and the free form results from the degradation of this protein. The eIF5A protein is the only one described containing the hypusine residue, which is essential for its activity. The biological relevance of free hypusine is still unknown, although it was discovered in the '70s. In fact, we have found interesting results with rat glioma cells (C6) after treatment with hypusine. The treatment significantly reduces the proliferation rate of these cells without a significant induction of apoptosis. Curiously, we observed a decrease in about half the number of cells compared to the control without any alteration of the cell cycle profile or protein synthesis rate. We performed a colony-forming assay, in which we observed suppression of colony formation by hypusine treatment. The ability of cells to proliferate in colony-forming assays is used to verify whether a treatment can reduce the clonogenic capacity of tumor cells. Based on our findings, now we are interested to perform a high throughput screening to find out which signaling pathways are related to the observed effects. To evaluate this, we are proposing a transcriptome analysis by next-generation RNA sequencing. Furthermore, the experience abroad will greatly contribute to my academic development and will also consolidate the internationalization of our laboratory, which enables important exchanges among the universities.