Abstract
Interleukin (IL)-36α, a newly recognized IL-1 family member, has been previously reported to play a pivotal role in autoimmunity diseases and acute inflammatory reactions. Recently, several studies have indicated that IL-36α has potential anticancer effects against certain types of cancer. However, the expression pattern and functional role of IL-36α in non-small cell lung cancer (NSCLC) have not been elucidated. Here, we report that the mRNA and protein levels of IL-36α are significantly reduced in NSCLC tissues. Low levels of intratumoral IL-36α are correlated with higher tumor status, advanced TNM stage, increased vascular invasion and shorter overall survival (OS). Intratumoral IL-36α expression is an independent prognostic factor for OS (hazard ratio = 3.081; P = 0.012) in patients with NSCLC. Overexpression of IL-36α in lung cancer cells did not disturb cell proliferation, apoptosis or cell-cycle distribution in vitro, but markedly inhibited tumor growth in vivo. Mechanistically, IL-36α reduced the expression and secretion of vascular endothelial growth factor A through inhibiting hypoxia-inducible factor 1α expression. Finally, decreased IL-36α expression was associated with high microvessel density and vascular endothelial growth factor A in patients with NSCLC. Together, our findings suggest that IL-36α expression is a valuable marker indicating poor prognosis in patients with NSCLC.