The role of Nek4 and its mutations in the modulation of gene expression in lung cancer

• Grant number: 24/22039-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2025
• End date: February 28, 2029
• 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: 22/15126-9 - Two cell cycle regulatroy protein families: from functional studies to their use as novel diagnostic markers and therapeutic targets in cancer, AP.TEM

Abstract

Lung cancer is the leading cause of cancer-related death and the second most diagnosed cancer worldwide. Nek4 is a serine/threonine kinase that has been associated with important cellular mechanisms, such as microtubule formation, apoptosis, replicative senescence, epithelial-to-mesenchymal transition (EMT), mitochondrial regulation, and DNA damage response (DDR). Recent unpublished results from our laboratory suggest that Nek4 may influence gene expression and alternative splicing regulation in lung cancer cells. However, the mechanisms by which Nek4 acts are still unknown. This project aims to investigate the role of Nek4 in gene expression modulation, focusing on genes related to apoptosis and DNA damage response in lung cancer. To this end, we will investigate potential interactions between Nek4 and transcription and splicing factors, an evaluate its phosphorylation by Nek4. We will also evaluate functional consequences in apoptosis, DNA damage response, and alternative splicing for different expressions of Nek4 and its mutants, as well as with alternative splicing modulators. Additionally, the study with patient samples will allow for an exploratory study of Nek4 and its variants, as well as the expression of genes potentially regulated by Nek4. By elucidating these mechanisms, this study aims to contribute to a more comprehensive understanding of the role of Nek4 in tumor progression and treatment response, offering new perspectives on potential therapeutic targets in lung cancer. (AU)