Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China; Department of Laboratory Medicine, The Second People's Hospital of Guizhou Province, Guiyang, 550004, China.
Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China; Department of Clinical Laboratory, The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, 550001, China; Division of Gastroenterology and Hepatology, Department of Medicine and Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Biochem Biophys Res Commun. 2023 Dec 31;689:149188. doi: 10.1016/j.bbrc.2023.149188. Epub 2023 Nov 7.
This study focused on exploring the mechanism of the EMT mediated by endonuclease/exonuclease/phosphatase family domain-containing 1 (EEPD1) in gastric cancer metastasis. Through bioinformatics analysis, EEPD1 was found to be a target gene of super enhancers (SEs) in gastric cancer tissues. EEPD1 exhibited higher expression levels in tumor tissues and was associated with poor prognosis. In vitro and in vivo studies have demonstrated that silencing EEPD1 significantly suppressed the proliferation, metastasis, and invasion of gastric cancer cells. Furthermore, EEPD1 knockdown was involved in the regulation of the EMT and suppressed expression of AKT, a downstream component of the PI3K pathway, leading to a reduction in the phosphorylation levels of AKT and its downstream molecule, mTOR. These results showed the potential of EEPD1 as a prognostic indicator and therapeutic target in gastric cancer.
本研究旨在探讨内切核酸酶/外切核酸酶/磷酸酶家族结构域包含蛋白 1（EEPD1）在胃癌转移中介导 EMT 的机制。通过生物信息学分析，发现 EEPD1 是胃癌组织中超增强子（SEs）的靶基因。EEPD1 在肿瘤组织中表达水平较高，与预后不良相关。体外和体内研究表明，沉默 EEPD1 可显著抑制胃癌细胞的增殖、转移和侵袭。此外，EEPD1 敲低参与 EMT 的调节，并抑制 PI3K 通路下游分子 AKT 的表达，导致 AKT 及其下游分子 mTOR 的磷酸化水平降低。这些结果表明 EEPD1 作为胃癌的预后指标和治疗靶点具有潜力。
