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| Verfasst von: | Baranašić, Jurica [VerfasserIn]  |
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| | Šutić, Maja [VerfasserIn] |
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| | Catalano, Calogerina [VerfasserIn] |
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| | Drpa, Gordana [VerfasserIn] |
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| | Huhn, Stefanie [VerfasserIn] |
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| | Majhen, Dragomira [VerfasserIn] |
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| | Nestić, Davor [VerfasserIn] |
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| | Kurtović, Matea [VerfasserIn] |
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| | Rumora, Lada [VerfasserIn] |
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| | Bosnar, Martina [VerfasserIn] |
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| | Vukić Dugac, Andrea [VerfasserIn] |
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| | Sokolović, Irena [VerfasserIn] |
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| | Popovic-Grle, Sanja [VerfasserIn] |
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| | Oršolić, Nada [VerfasserIn] |
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| | Škrinjarić-Cincar, Sanda [VerfasserIn] |
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| | Jakopović, Marko [VerfasserIn] |
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| | Samaržija, Miroslav [VerfasserIn] |
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| | Weber, Alexander N. R. [VerfasserIn] |
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| | Försti, Asta [VerfasserIn] |
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| | Knežević, Jelena [VerfasserIn] |
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| Titel: | TLR5 variants are associated with the risk for COPD and NSCLC development, better overall survival of the NSCLC patients and increased chemosensitivity in the H1299 cell line |
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| Verf.angabe: | Jurica Baranašić, Maja Šutić, Calogerina Catalano, Gordana Drpa, Stefanie Huhn, Dragomira Majhen, Davor Nestić, Matea Kurtović, Lada Rumora, Martina Bosnar, Andrea Vukić Dugac, Irena Sokolović, Sanja Popovic-Grle, Nada Oršolić, Sanda Škrinjarić-Cincar, Marko Jakopović, Miroslav Samaržija, Alexander N. R. Weber, Asta Försti and Jelena Knežević |
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| E-Jahr: | 2022 |
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| Jahr: | 9 September 2022 |
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| Umfang: | 23 S. |
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| Fussnoten: | Gesehen am 04.11.2022 |
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| Titel Quelle: | Enthalten in: Biomedicines |
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| Ort Quelle: | Basel : MDPI, 2013 |
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| Jahr Quelle: | 2022 |
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| Band/Heft Quelle: | 10(2022), 9, Artikel-ID 2240, Seite 1-23 |
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| ISSN Quelle: | 2227-9059 |
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| Abstract: | Chronic obstructive pulmonary disease (COPD) is considered as the strongest independent risk factor for lung cancer (LC) development, suggesting an overlapping genetic background in both diseases. A common feature of both diseases is aberrant immunity in respiratory epithelia that is mainly regulated by Toll-like receptors (TLRs), key regulators of innate immunity. The function of the flagellin-sensing TLR5 in airway epithelia and pathophysiology of COPD and LC has remained elusive. We performed case-control genetic association and functional studies on the importance of TLR5 in COPD and LC development, comparing Caucasian COPD/LC patients (n = 974) and healthy donors (n = 1283). Association analysis of three single nucleotide polymorphisms (SNPs) (rs725084, rs2072493_N592S, and rs5744174_F616L) indicated the minor allele of rs2072493_N592S to be associated with increased risk for COPD (OR = 4.41, p < 0.0001) and NSCLC (OR = 5.17, p < 0.0001) development and non-small cell LC risk in the presence of COPD (OR = 1.75, p = 0.0031). The presence of minor alleles (rs5744174 and rs725084) in a co-dominant model was associated with overall survival in squamous cell LC patients. Functional analysis indicated that overexpression of the rs2072493_N592S allele affected the activation of NF-κB and AP-1, which could be attributed to impaired phosphorylation of p38 and ERK. Overexpression of TLR5N592S was associated with increased chemosensitivity in the H1299 cell line. Finally, genome-wide transcriptomic analysis on WI-38 and H1299 cells overexpressing TLR5WT or TLR5N592S, respectively, indicated the existence of different transcription profiles affecting several cellular pathways potentially associated with a dysregulated immune response. Our results suggest that TLR5 could be recognized as a potential biomarker for COPD and LC development with functional relevance. |
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| DOI: | doi:10.3390/biomedicines10092240 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: https://doi.org/10.3390/biomedicines10092240 |
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| | Volltext: https://www.mdpi.com/2227-9059/10/9/2240 |
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| | DOI: https://doi.org/10.3390/biomedicines10092240 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | chemoresistance |
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| | COPD |
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| | NSCLC |
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| | SNP |
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| | survival |
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| | TLR5 |
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| K10plus-PPN: | 1820724360 |
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| Verknüpfungen: | → Zeitschrift |
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TLR5 variants are associated with the risk for COPD and NSCLC development, better overall survival of the NSCLC patients and increased chemosensitivity in the H1299 cell line / Baranašić, Jurica [VerfasserIn]; 9 September 2022 (Online-Ressource)
