IL‑17 induces NSCLC A549 cell proliferation via the upregulation of HMGA1, resulting in an increased cyclin D1 expression

Non-small cell lung cancer (NSCLC) is considered to be an inflammation-associated carcinoma. Although interleukin‑17 (IL‑17) production contributes to the proliferation and growth of NSCLC, the mechanisms underlying IL‑17-induced NSCLC cell proliferation have not been fully elucidated. In the presen...

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Bibliographic Details
Published inInternational journal of oncology Vol. 52; no. 5; pp. 1579 - 1592
Main Authors Zhao, Chenhui, Li, Yongting, Zhang, Weiming, Zhao, Dan, Ma, Ling, Ma, Pei, Yang, Fengming, Wang, Yingwei, Shu, Yongqian, Qiu, Wen
Format Journal Article
LanguageEnglish
Published Greece Spandidos Publications 01.05.2018
Spandidos Publications UK Ltd
Subjects
Analysis
Cancer genetics
Cancer research
Cell growth
Cyclin D
Development and progression
Gene expression
Genetic aspects
Health aspects
Immunoglobulins
Interleukin-17
Lung cancer
Lymphatic system
Medical research
Metastasis
Non-small cell lung cancer
Transcription factors
United States > US
China
Germany
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Summary:Non-small cell lung cancer (NSCLC) is considered to be an inflammation-associated carcinoma. Although interleukin‑17 (IL‑17) production contributes to the proliferation and growth of NSCLC, the mechanisms underlying IL‑17-induced NSCLC cell proliferation have not been fully elucidated. In the present study, by using ELISA and immunohistochemical analyses, we first found that the expression levels of IL‑17, IL‑17 receptor (IL‑17R), high-mobility group A1 (HMGA1) and cyclin D1 were elevated in the samples of patients with NSCLC. Subsequently, by RT-qPCR, western blot analysis and cell proliferation assay in vitro, we revealed that stimulation with recombinant human IL‑17 (namely IL‑17A) markedly induced the expression of HMGA1 and cyclin D1 in the A549 cells (a human lung adenocarcinoma cell line) and promoted cell proliferation. Furthermore, luciferase reporter and ChIP assays confirmed that upregulated HMGA1 directly bound to the cyclin D1 gene promoter and activated its transcription. Notably, the response element of HMGA1 binding to the cyclin D1 promoter was disclosed for the first time, at least to the best of our knowledge. Taken together, our findings indicate that the IL‑17/HMGA1/cyclin D1 axis plays an important role in NSCLC cell proliferation and may provide new insight into NSCLC pathogenesis and may thus aid in the development of novel therapeutic targets for NSCLC.
ISSN:1019-6439
1791-2423
DOI:10.3892/ijo.2018.4307