Utjecaj polimorfizama TLR5 (rs2072493) i TLR7 (rs5935436) na transkriptom i metabolom u staničnom modelu karcinoma pluća nemalih stanica

Baranašić, Jurica (2023) Utjecaj polimorfizama TLR5 (rs2072493) i TLR7 (rs5935436) na transkriptom i metabolom u staničnom modelu karcinoma pluća nemalih stanica. Doctoral thesis, Sveučilište u Zagrebu, Prirodoslovno-matematički fakultet.

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Abstract

Lung cancer is one of the leading causes of cancer-related deaths worldwide. Exposure to smoke is the main cause of developing lung cancer, genetic background also has a significant role. Activation of Toll-like receptors (TLR) starts a complex signaling pathway, which in the end releases transcriptional factors. Previous associations studies linked polymorphisms in TLR5 (rs2072493) and TLR7 (rs5935436) with higher susceptibility of developing lung cancer. The aim of this research was to examine the effect of these polymorphisms on the transcriptome and metabolome in vitro. The results of the transcriptome analysis show that the rs2072493 polymorphism affects changes in the activity of the G protein-coupled receptor (GPCR) signaling pathway. The results of the metabolome analysis show that the presence of the rs2072493 polymorphism changes the activity of tryptophan metabolism. Furthermore, metastatic lung cancer cells, H1299, overexpressing TLR7 are more sensitive to co-treatment with imiquimod and paclitaxel. Also, the change in TLR7 expression affects the activity of glycolysis metabolism, the HIF-1 signaling pathway, and the AMPK signaling pathway.

Item Type:

Thesis (Doctoral thesis)

Uncontrolled Keywords:

lung cancer; polymorphisms; TLR5; TLR7; immune response

Subjects:

BIOMEDICINE AND HEALTHCARE
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Human Genetics, Genomics and Proteomics
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences > Immunology

Divisions:

Division of Molecular Medicine

Projects: