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

Abstract

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.

Long-term PM2.5 exposure increases the risk of non-small cell lung cancer (NSCLC) progression by enhancing interleukin-17a (IL-17a)-regulated proliferation and metastasis

“…Long-term PM2.5 exposure is tightly associated with NSCLC progression. Increasing studies have shown the importance of IL-17a in promoting tumor development, including NSCLC, via multiple mechanisms [23][24][25][26][27][28][29]. In this research, chronic PM2.5 exposure at high dose caused significant pulmonary damage and fibrosis.…”

“…Th17 cells are enriched within peripheral blood mononuclear cells and tumor tissues. IL-17a is mainly produced by Th17 cells, which is closely associated with the development of various types of tumors, including lung cancer [ 26 – 28 , 50 ]. Elevated IL-17-producing cells were involved in the poor survival and lymphangiogenesis in NSCLC patients [ 51 ].…”

“…Tumor-infiltrating Th17 cells were detected in human colorectal cancer, which were associated with shortened disease-free survival [ 25 ]. In addition, IL-17 might be implicated in the metastasis of NSCLC through promoting lymphangiogenesis [ 26 ]. Recent analysis also indicated that IL-17 might be a critical cytokine involved in the progression of NSCLC.…”

HMGA1 Modulates Gene Transcription Sustaining a Tumor Signalling Pathway Acting on the Epigenetic Status of Triple-Negative Breast Cancer Cells

“…In addition, RSK2 has a prominent role in the activation of the transcription factor Y-box binding protein-1 (YB-1) which is a main factor leading to the development of basal-like cancer [69,96,97]. Albeit in a different cellular model, i.e., in non-small-cell lung cancer (NSCLC) cells A549, it is intriguing that both HMGA1 and YB-1 have been demonstrated to bind to the promoter of cyclin D1 and to be responsible for its transcriptional regulation [98,99]. In breast cancer cells it was demonstrated that chromatin remodelling is upstream of YB-1 landing onto promoters [97].…”

Depression Accelerates Tumor Cell Proliferation Via Regulating Serotonin/miR-144 Axis in NSCLC Mice

“…It has been reported that around 85% patients with lung cancer were diagnosed as NSCLC [2], suggesting its urgent need in promising therapeutic treatment. Various risk factors accelerates the progression of NSCLC, promoting its tumor proliferation, including inflammation [3], oxidation [4], and also, the psychiatric factors, such as depression [5,6].…”