Decreased interleukin-17RA expression is associated with good prognosis in patients with colorectal cancer and inhibits tumor growth and vascularity in mice
© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd..
BACKGROUND: Interleukin-17 (IL-17) is a pro-inflammatory cytokine that plays a vital role in the promotion of tumorigenesis in various cancers, including colorectal cancer (CRC). Based on current evidence, IL-17 binds to interleukin-17 receptor A (IL-17RA); however, the role of IL-17RA has not been elucidated in previous studies on CRC. In this study, we explored the role of IL-17RA in human CRC tissues and the progression of CRC in humans and mice.
METHODS: The expressions of IL-17RA and epithelial-mesenchymal transition (EMT)-related genes were examined in CRC cells and tissue samples by quantitative real-time polymerase chain reaction. The role of IL-17RA in pathogenesis and prognosis was evaluated using a Chi-squared test, Kaplan-Meier analysis, univariate, and multivariate Cox regression analysis in 133 CRC patients. A tumor-bearing mice model was executed to evaluate the role of IL-17RA in tumor growth, vascularity and population of infiltrating immune cells.
RESULTS: IL-17RA expression was found to be significantly higher in CRC tissues than in adjacent normal tissues. The expression of IL-17RA in Stage IV patients was significantly higher than that in Stages I and II patients. Patients with high IL-17RA expression exhibited significantly worse overall and CRC-specific survival than those with low IL-17RA expression. Functional assessment suggested that the knockdown of IL-17RA expression distinctly suppressed cellular proliferation, migration, invasion, and EMT-related gene expression. In a tumor-bearing mouse model, decreased IL-17RA expression significantly repressed tumor growth and vascularity and reduced the population of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs).
CONCLUSION: Reduced IL-17RA expression also suppressed cellular proliferation, migration, and invasion, and the expression of EMT genes. Knockdown of IL-17RA inhibited tumor growth and vascularity and decreased the population of Tregs and MDSCs in mouse tumors. Overall, IL-17RA expression was identified to be independently associated with the prognosis of patients with CRC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Cancer medicine - 13(2024), 5 vom: 31. März, Seite e7059 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jiang, Jeng-Kai [VerfasserIn] |
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| Links: |
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| Themen: |
Colorectal cancer |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 18.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/cam4.7059 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369815106 |
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| 100 | 1 | |a Jiang, Jeng-Kai |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Decreased interleukin-17RA expression is associated with good prognosis in patients with colorectal cancer and inhibits tumor growth and vascularity in mice |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND: Interleukin-17 (IL-17) is a pro-inflammatory cytokine that plays a vital role in the promotion of tumorigenesis in various cancers, including colorectal cancer (CRC). Based on current evidence, IL-17 binds to interleukin-17 receptor A (IL-17RA); however, the role of IL-17RA has not been elucidated in previous studies on CRC. In this study, we explored the role of IL-17RA in human CRC tissues and the progression of CRC in humans and mice | ||
| 520 | |a METHODS: The expressions of IL-17RA and epithelial-mesenchymal transition (EMT)-related genes were examined in CRC cells and tissue samples by quantitative real-time polymerase chain reaction. The role of IL-17RA in pathogenesis and prognosis was evaluated using a Chi-squared test, Kaplan-Meier analysis, univariate, and multivariate Cox regression analysis in 133 CRC patients. A tumor-bearing mice model was executed to evaluate the role of IL-17RA in tumor growth, vascularity and population of infiltrating immune cells | ||
| 520 | |a RESULTS: IL-17RA expression was found to be significantly higher in CRC tissues than in adjacent normal tissues. The expression of IL-17RA in Stage IV patients was significantly higher than that in Stages I and II patients. Patients with high IL-17RA expression exhibited significantly worse overall and CRC-specific survival than those with low IL-17RA expression. Functional assessment suggested that the knockdown of IL-17RA expression distinctly suppressed cellular proliferation, migration, invasion, and EMT-related gene expression. In a tumor-bearing mouse model, decreased IL-17RA expression significantly repressed tumor growth and vascularity and reduced the population of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) | ||
| 520 | |a CONCLUSION: Reduced IL-17RA expression also suppressed cellular proliferation, migration, and invasion, and the expression of EMT genes. Knockdown of IL-17RA inhibited tumor growth and vascularity and decreased the population of Tregs and MDSCs in mouse tumors. Overall, IL-17RA expression was identified to be independently associated with the prognosis of patients with CRC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a colorectal cancer | |
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| 700 | 1 | |a Lin, Chi-Hung |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Ting-An |e verfasserin |4 aut | |
| 700 | 1 | |a Lo, Liang-Chuan |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Chien-Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Ruey-Hwa |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Chih-Yung |e verfasserin |4 aut | |
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