Research Center of Clinical Epidemiology, Peking University Third Hospital, 100191, Beijing, PR China.
Department of Clinical Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, 110001, Liaoning, PR China.
Cell Death Dis. 2019 Aug 19;10(9):625. doi: 10.1038/s41419-019-1859-8.
Gastric cancer is an important cause of death worldwide with Helicobacter pylori (H. pylori) considered a leading and known risk factor for its development. More particularly and despite the underlying mechanisms not being very clear, studies have revealed that the H. pylori cytotoxin-associated gene A (CagA) protein plays a key role in this process. In this study it was found that H. pylori increased the expression of miR-543 in human gastric cancer tissue when compared with H. pylori-negative gastric cancer tissue samples. In vitro experiments showed that increased expression of miR-543 induced by CagA is a strong promoter of cell proliferation, migration, and invasion. Conversely, a miR-543 inhibitor suppressed or reversed these effects. It was furthermore found that silencing miR-543 inhibited autophagy and led to epithelial-mesenchymal transition (EMT) under in vitro. The mechanisms by which miR-543 targets SIRT1 to downregulate autophagy was also described. The results suggest that in the progression of H. pylori-associated gastric cancer, CagA induces overexpression of miR-543, which subsequently targets SIRT1 to suppress autophagy. This may be followed by increased expression of EMT causing cell migration and invasion. Consequently, miR-543 might be considered a therapeutic target for H. pylori-associated gastric cancer.
胃癌是全球范围内一个重要的死亡原因，幽门螺杆菌（H. pylori）被认为是其发展的主要和已知的危险因素。更具体地说，尽管潜在的机制尚不清楚，但研究表明，幽门螺杆菌细胞毒素相关基因 A（CagA）蛋白在这一过程中起着关键作用。在这项研究中发现，与幽门螺杆菌阴性胃癌组织样本相比，幽门螺杆菌在人胃癌组织中增加了 miR-543 的表达。体外实验表明，CagA 诱导的 miR-543 表达增加是细胞增殖、迁移和侵袭的强烈促进剂。相反，miR-543 抑制剂抑制或逆转了这些作用。此外，还发现沉默 miR-543 在体外抑制自噬并导致上皮-间充质转化（EMT）。miR-543 靶向 SIRT1 下调自噬的机制也被描述。研究结果表明，在幽门螺杆菌相关胃癌的进展过程中，CagA 诱导 miR-543 的过度表达，随后靶向 SIRT1 抑制自噬。这可能导致 EMT 的表达增加，从而引起细胞迁移和侵袭。因此，miR-543 可能被视为与幽门螺杆菌相关的胃癌的治疗靶点。
