GM130通过调控snail表达调节胃癌上皮间质化过程

GM130 Regulates Gastric Epithelial Mesenchymal Transition Through Regulating Snail Expression

目的胃癌是最常见的消化道肿瘤之一。尽管手术和放化疗发展迅速,但胃癌的潜在作用机制仍知之甚少,相关的基因及分子治疗值得继续探索。近些年,越来越多的研究显示上皮细胞间质化(EMT)是胃癌侵袭转移的一个重要环节,其作用机制尚不清楚。GM130是顺式高尔基体的基质蛋白,在细胞周期和蛋白质的运输、分泌过程中扮演着重要的角色。方法免疫组化检测GM130在胃癌组织中的表达情况,在胃癌细胞中采用siRNA技术沉默其表达,观察生物学功能的变化。结果在本研究中,我们发现GM130的表达与胃癌的肿瘤分化和TNM分期有关。GM130的高表达预示着较差的预后。运用RNA干扰技术敲低GM130表达后,我们发现上皮标志物E-cadherin表达增加,间质标记物N-cadherin和vimentin表达减少,肿瘤的发生发展被抑制。减少(N-cadherin和波形蛋白)表达锡安在胃癌细胞,抑制细胞入侵和肿瘤的形成。此外,我们还发现GM130通过上调EMT的关键分子Snail(SNAI1)参与胃癌EMT及侵袭转移的过程。结论本研究显示GM130可能是胃癌治疗中的一个新的靶点。

Objective Gastric cancer is one of the most common causes of digestive tract tumor. Despite of recent advances in surgical techniques and development of adjuvant therapy, the underlying mechanisms of gas-tric cancer remain poorly understood and relevant insight into novel treatment strategies using gene target re-mains incomplete. Re - cently, several studies report that epithelial to mesenchymal transition （EMT） is a cru-cial process for the invasion and metastasis of epithelial tumors; however, the molecular mechanisms underlying this transition are unknown. Methods As a cis - Golgi matrix protein, GM130 plays an important role in cell cycle progression and transport of protein in the secretory pathway. Results In this study, we found that GM130 expression has a positive correlation with the pathological differentiation and tumor node metastasis （TNM） stage of gastric cancer. High GM130 expression levels also predict shorter overall survival of gastric can-cer patients. RNA interference - mediated knockdown of GM130 expression increased epithelial marker （E - cadherin） and decreased mesenchymal marker （N - cadherin and vimentin） exp res - sion in gastric cancer cells, suppressing cell invasion, and tumor formation. Furthermore, we found that GM130 up regulated expression of the key EMT regulator Snail （SNAl l） ,which mediated EMT activation and cell invasion by GM130. Conclu-sion Taken together, our study indicates GM130 may be a promising therapeutic biomarker for gastric cancer.