长链非编码RNA ZNF667-AS1通过沉默N-钙黏蛋白和血管内皮生长因子A的表达来抑制胃癌的增殖、侵袭和血管生成。
The lncRNA ZNF667-AS1 Inhibits Propagation, Invasion, and Angiogenesis of Gastric Cancer by Silencing the Expression of N-Cadherin and VEGFA.
作者信息
Yu Chong, Chen Wenqian, Cai Yi, Du Mingyu, Zong Dan, Qian Luxi, Jiang Xuesong, Zhu Huanfeng
机构信息
Department of Radiation Oncology, Changshu Hospital Affiliated to Soochow University, Changshu No. 1 People's Hospital, Changshu 215500, Jiangsu, China.
Department of Medical Oncology, Changshu Hospital Affiliated to Soochow University, Changshu No. 1 People's Hospital, Changshu 215500, Jiangsu, China.
出版信息
J Oncol. 2022 Jul 1;2022:3579547. doi: 10.1155/2022/3579547. eCollection 2022.
PURPOSE
Gastric cancer is one of the most common malignancies with high mortality worldwide. It is known that long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of gastric cancer. This study investigates the role of lncRNA ZNF667-AS1 in gastric cancer cells.
METHODS
We have applied real-time quantitative PCR (qPCR) to study the levels of ZNF667-AS1 in gastric cancer biopsies and cell lines. The effects of ZNF667-AS1 on the propagation, clonogenicity, metastasis, and angiogenesis of gastric cancer cells were evaluated by calorimetry, colony formation, cell migration, and angiogenesis assays. Western blotting was used to identify the levels of proteins involved in cancer invasion and angiogenesis signaling pathways.
RESULT
It was found that lncRNA ZNF667-AS1 was downregulated in gastric cancer biopsies. Overexpression of ZNF667-AS1 reduced the propagation, migration, and angiogenesis of gastric cancer cells. Molecular mechanism studies displayed that the high level of lncRNA ZNF667-AS1 promoted the expression of E-cadherin and inhibited the expression of N-cadherin and VEGFA, leading to the inhibition of the proliferation, migration, and angiogenesis of gastric cancer cells.
CONCLUSION
As a tumor suppressor gene, lncRNA ZNF667-AS1 significantly hinders the propagation, metastasis, and angiogenesis of gastric cancer cells by promoting the expression of E-cadherin and inhibiting the expression of N-cadherin and VEGFA. Therefore, lncRNA ZNF667-AS1 could play a synergistic therapeutic role by targeting tumor cells and vascular endothelial cells, which represents a new therapeutic scheme for novel therapeutics of gastric cancer.
目的
胃癌是全球最常见且死亡率高的恶性肿瘤之一。已知长链非编码RNA（lncRNA）在胃癌发病机制中发挥重要作用。本研究探讨lncRNA ZNF667 - AS1在胃癌细胞中的作用。
方法
我们应用实时定量聚合酶链反应（qPCR）研究lncRNA ZNF667 - AS1在胃癌活检组织和细胞系中的水平。通过比色法、集落形成、细胞迁移和血管生成实验评估ZNF667 - AS1对胃癌细胞增殖、克隆形成、转移和血管生成的影响。采用蛋白质免疫印迹法鉴定参与癌症侵袭和血管生成信号通路的蛋白质水平。
结果
发现lncRNA ZNF667 - AS1在胃癌活检组织中表达下调。ZNF667 - AS1的过表达降低了胃癌细胞的增殖、迁移和血管生成。分子机制研究表明，高水平的lncRNA ZNF667 - AS1促进E - 钙黏蛋白的表达，抑制N - 钙黏蛋白和血管内皮生长因子A（VEGFA）的表达，导致胃癌细胞增殖、迁移和血管生成受到抑制。
结论
作为一种肿瘤抑制基因，lncRNA ZNF667 - AS1通过促进E - 钙黏蛋白的表达和抑制N - 钙黏蛋白及VEGFA的表达，显著阻碍胃癌细胞的增殖、转移和血管生成。因此，lncRNA ZNF667 - AS1可通过靶向肿瘤细胞和血管内皮细胞发挥协同治疗作用，这代表了一种新的胃癌治疗方案。
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