Interleukin-17A in the Pathogenesis of Lung Adenocarcinoma

Zhen Lin, Christian Nguyen, Beibei Xu, Erik K. Flemington, Gilbert F. Morris

Research output: Contribution to journalArticle

Abstract

RATIONALE: Evidence has shown that inhaled lung carcinogens, such as tobacco smoke, silica, or asbestos, induce a T-helper cell type 17 inflammatory environment. Interleukin-17A (commonly and hereafter called IL-17) is the signature cytokine of T-helper cell type 17 inflammation. We have shown previously that IL-17 overexpression promotes growth of lung adenocarcinoma in transgenic mouse models. Our additional findings suggest that IL-17 suppresses the function of the p53 tumor suppressor protein in a mutant K-Ras-expressing lung tumor cell line. OBJECTIVES: To compare our studies in mice to clinical samples. METHODS: We have used informatics and RNA sequencing-based approaches to analyze primary human lung adenocarcinoma samples. RESULTS: Comprehensive transcriptome analyses have shown that IL-17 expression positively correlates with expression of serine/arginine-rich splicing factor 1 (SRSF1), a key cellular splicing factor. This observation correlates with our previous finding that IL-17 regulates the activity of serine/argininerich splicing factor 1. In accord, there are significant differences in the global splicing activity between the IL-17+ and IL-17- lung adenocarcinomas, indicating that IL-17 may affect the selectivity of RNA splicing events by targeting serine/argininerich splicing factor 1. Further, Ingenuity pathway analyses (Qiagen) have identified activation of key pathways in IL-17+ relative to IL17- lung adenocarcinomas. In these analyses, IL-18 signaling appears central to IL-17+ lung adenocarcinomas, which display prominent signatures related to inflammation and evasion of antitumor immunity. CONCLUSIONS: Our RNA sequencing-based transcriptome analyses of lung adenocarcinomas have identified a cohort of patients that may be good candidates for immune therapy.

Original languageEnglish (US)
Pages (from-to)S125
JournalAnnals of the American Thoracic Society
Volume15
Issue number2
DOIs
StatePublished - Apr 1 2018

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Interleukin-17
RNA Sequence Analysis
Th17 Cells
Gene Expression Profiling
Serine
Adenocarcinoma of lung
Inflammation
RNA Splicing
Tumor Suppressor Protein p53
Lung
Interleukin-18
Informatics
Asbestos
Tumor Cell Line
Smoke
Silicon Dioxide
Carcinogens
Transgenic Mice
Tobacco
Immunity

Keywords

  • IL-17A
  • K-Ras
  • T-helper cell type 17 inflammation
  • lung adenocarcinoma
  • lung inflammation

Cite this

Interleukin-17A in the Pathogenesis of Lung Adenocarcinoma. / Lin, Zhen; Nguyen, Christian; Xu, Beibei; Flemington, Erik K.; Morris, Gilbert F.

In: Annals of the American Thoracic Society, Vol. 15, No. 2, 01.04.2018, p. S125.

Research output: Contribution to journalArticle

Lin, Zhen ; Nguyen, Christian ; Xu, Beibei ; Flemington, Erik K. ; Morris, Gilbert F. / Interleukin-17A in the Pathogenesis of Lung Adenocarcinoma. In: Annals of the American Thoracic Society. 2018 ; Vol. 15, No. 2. pp. S125.
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abstract = "RATIONALE: Evidence has shown that inhaled lung carcinogens, such as tobacco smoke, silica, or asbestos, induce a T-helper cell type 17 inflammatory environment. Interleukin-17A (commonly and hereafter called IL-17) is the signature cytokine of T-helper cell type 17 inflammation. We have shown previously that IL-17 overexpression promotes growth of lung adenocarcinoma in transgenic mouse models. Our additional findings suggest that IL-17 suppresses the function of the p53 tumor suppressor protein in a mutant K-Ras-expressing lung tumor cell line. OBJECTIVES: To compare our studies in mice to clinical samples. METHODS: We have used informatics and RNA sequencing-based approaches to analyze primary human lung adenocarcinoma samples. RESULTS: Comprehensive transcriptome analyses have shown that IL-17 expression positively correlates with expression of serine/arginine-rich splicing factor 1 (SRSF1), a key cellular splicing factor. This observation correlates with our previous finding that IL-17 regulates the activity of serine/argininerich splicing factor 1. In accord, there are significant differences in the global splicing activity between the IL-17+ and IL-17- lung adenocarcinomas, indicating that IL-17 may affect the selectivity of RNA splicing events by targeting serine/argininerich splicing factor 1. Further, Ingenuity pathway analyses (Qiagen) have identified activation of key pathways in IL-17+ relative to IL17- lung adenocarcinomas. In these analyses, IL-18 signaling appears central to IL-17+ lung adenocarcinomas, which display prominent signatures related to inflammation and evasion of antitumor immunity. CONCLUSIONS: Our RNA sequencing-based transcriptome analyses of lung adenocarcinomas have identified a cohort of patients that may be good candidates for immune therapy.",
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