Investigation of the regulatory role of Nek4 in the alternative splicing in non-small cell lung cancer

• Grant number: 21/09439-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: May 01, 2022
• End date: May 31, 2024
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Jörg Kobarg
• Grantee: Lívia Alves dos Reis Moura
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 17/03489-1 - From functional studies to searching for new inhibitors for cancer: exploring kinases that regulate the cell cycle of the human NEK family, AP.TEM
• Associated scholarship(s): 23/01055-5 - Evaluation of alternative splicing profile regulated by Nek4 isoforms, BE.EP.MS

Abstract

Nek4 is a serine-threonine kinase from the Nek family that, among other functions, has a role in mRNA alternative splicing regulation. The mechanism of this regulation is not clear so far, but it is known that both Nek4 isoforms interact with numerous splicing factors. The alternative splicing of specific genes are frequently dysregulated in cancer, affecting cancer development and progression and playing a significant role in chemotherapy response and radiation resistance. Nek4 is a positive regulator of epithelialtomesenchymal transition in pulmonary cancer, and its high levels are associated with chemoresistance. Our preliminary results indicate that Nek4 overexpressing cells show an increase in anti-apoptotic isoforms after etoposide treatment, a common drug used for lung cancer treatment. The expression of Nek4 is altered in many types of cancer, particularly in lung and colon cancer. This project aims to assess whether Nek4 regulates alternative splicing in lung cancer cells in response to chemotherapy.