Correlation between serum IL-1β and miR-144-3p as well as their prognostic values in LUAD and LUSC patients

Oncotarget. 2016 Dec 27;7(52):85876-85887. doi: 10.18632/oncotarget.13042.

Abstract

Background: IL-1β is an essential factor of inflammation initiation, and it also promotes malignant transformation, indicating its tumorigenic property. We aimed to investigate the correlation between IL-1β and miR-144-3p as well as their prognostic values in LUAD and LUSC patients.

Results: The IL-1β level in both LUAD and LUSC patients was significantly higher than that of healthy donors (P < 0.001). In both populations, patients with low IL-1β level had better prognosis than high IL-1β level (P < 0.001 and P = 0.010, respectively). In A549 cells, miR-144 showed the biggest expression change (-4.38 fold) after IL-1β exposure. In LUAD patients, a negative correlation was detected between IL-1β and miR-144-3p (r = -0.540, P < 0.001) and the high miR-144-3p group had better prognosis (P = 0.003), which was validated by TCGA data. Clinical stage, IL-1β and miR-144-3p were independent risk factors in LUAD patients. In vitro, IL-1β and miR-144-3p antagomir could enhance proliferation and miR-144-3p mimics would attenuate the promoting effect of IL-1β.

Materials and methods: ELISA and qRT-PCR were applied respectively to detected cytokines and miR-144-3p in 129 LUAD, 54 LUSC and 40 healthy donors. Moreover, miRNA array was carried out for miRNA profiling. TCGA database was employed for validation, and follow up data were collected for prognosis evaluation. MTT assay and western-blot were carried out for proliferation evaluation.

Conclusions: In LUAD patients, the serum IL-1β level was correlated with miR-144-3p may affect miR-144-3p at transcriptional level. Both of them were independent risk factors for LUAD prognosis. In addition, IL-1β and miR-144-3p might mediate inflammation-promoted tumorigenesis in LUAD patients.

Keywords: IL-1β; LUAD; LUSC; miR-144-3p; prognosis.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / immunology
  • Adenocarcinoma / mortality*
  • Adenocarcinoma of Lung
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / mortality*
  • Cytokines / blood
  • Female
  • Humans
  • Interleukin-1beta / blood*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Lung Neoplasms / mortality*
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Prognosis

Substances

  • Cytokines
  • Interleukin-1beta
  • MIRN144 microRNA, human
  • MicroRNAs