Evaluation of alternative splicing profile regulated by Nek4 isoforms

• Grant number: 23/01055-5
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: May 01, 2023
• End date: October 31, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Jörg Kobarg
• Grantee: Lívia Alves dos Reis Moura
• Supervisor: Claudio Sette
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Università Cattolica del Sacro Cuore, di Roma, Italy
• Associated to the scholarship: 21/09439-1 - Investigation of the regulatory role of Nek4 in the alternative splicing in non-small cell lung cancer, BP.MS

Abstract

Nek4 is a serine-threonine kinase from the Nek family that, among other functions, has a role inmRNA alternative splicing regulation. The mechanism of this regulation is not clear so far, but it isknown that both Nek4 isoforms interact with numerous splicing factors. The alternative splicing ofspecific genes are frequently dysregulated in cancer, affecting cancer development and progressionand playing a significant role in chemotherapy response and radiation resistance. Nek4 is a positiveregulator of epithelial-mesenchymal transition in pulmonary cancer, and its high levels are associatedwith chemoresistance. Our preliminary results indicate that Nek4 overexpressing cells show anincrease in anti-apoptotic isoforms after etoposide treatment, a common drug used for lung cancertreatment. This project aims to assess whether Nek4 regulates alternative splicing by analyzingchanges on the transcriptome from cells either expressing one of the Nek4 isoforms or cells with thekinase dead mutant, all through high-throughput RNA sequencing (RNA-seq) and bioinformaticanalysis. The changes in the transcriptomes induced by Nek4 will allow us to identify the splicingevents regulated by Nek4 and investigate its impact in the chemotherapy resistance in lung cancercells.