Expression of HAb18G in non-small lung cancer and characterization of activation, migration, proliferation, and apoptosis in A549 cells following siRNA-induced downregulation of HAb18G.

ABSTRACT

HAb18G, a novel cancer biomarker, has been shown to be involved in the progression of malignancy by regulating expression of vascular endothelial growth factor (VEGF) and matrixmetalloproteinases (MMPs). The goal of this study was to evaluate the role of HAb18G in the biology of NSCLC and to determine its potential as a therapeutic target. HAb18G protein expression was detected by immunohistochemistry in 150 NSCLC tissues. The results showed that HAb18G protein expression was associated with tumor diameter, lymph node status, tumor stage, and poor prognosis (P < 0.05). Multivariate analysis showed that HAb18G overexpression was an independent prognostic factor (HR, 3.713; 95 % CI, 1.114-12.373; P = 0.033). Transient infection of A549 lung cancer cells with small interfering RNA (SiRNA) against HAb18G efficiently inhibited the expression of HAb18G in A549 lung cancer cells at both mRNA and protein levels. Downregulation of HAb18G not only reduced MMP-2, MMP-9, and VEGF at mRNA and protein levels in A549 cells, but also inhibited fibroblasts to secrete MMP-2 and MMP-9 at mRNA level. Additionally, downregulation of HAb18G mRNA resulted in decreased migration, proliferation, and increased apoptosis of A549 in vitro. Our findings suggest that HAb18G overexpression plays an important role in progression of NSCLC and HAb18G may be a potential target of NSCLC therapy.