Department of Pathology, Nanfang Hosptial, Southern Medical University, Guangzhou, China.
Mol Cell Biochem. 2013 Nov;383(1-2):1-11. doi: 10.1007/s11010-013-1722-7. Epub 2013 Sep 8.
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.
HAb18G，一种新型的癌症生物标志物，通过调节血管内皮生长因子（VEGF）和基质金属蛋白酶（MMPs）的表达，被证明参与了恶性肿瘤的进展。本研究的目的是评估 HAb18G 在 NSCLC 生物学中的作用，并确定其作为治疗靶点的潜力。通过免疫组织化学法检测 150 例 NSCLC 组织中的 HAb18G 蛋白表达。结果表明，HAb18G 蛋白表达与肿瘤直径、淋巴结状态、肿瘤分期和预后不良相关（P < 0.05）。多因素分析显示，HAb18G 过表达是独立的预后因素（HR，3.713；95 % CI，1.114-12.373；P = 0.033）。瞬时感染 A549 肺癌细胞的小干扰 RNA（siRNA）针对 HAb18G 有效地抑制了 A549 肺癌细胞中 HAb18G 的表达，无论是在 mRNA 还是蛋白水平上。下调 HAb18G 不仅降低了 A549 细胞中 MMP-2、MMP-9 和 VEGF 的 mRNA 和蛋白水平，还抑制了成纤维细胞在 mRNA 水平上分泌 MMP-2 和 MMP-9。此外，下调 HAb18G mRNA 导致 A549 在体外的迁移、增殖减少和凋亡增加。我们的研究结果表明，HAb18G 过表达在 NSCLC 的进展中起着重要作用，HAb18G 可能是 NSCLC 治疗的潜在靶点。
