Super-enhancer-associated EEPD1 facilitates EMT-mediated metastasis by regulating the PI3K/AKT/mTOR pathway in gastric cancer

Yong Jin; Ying Xia; Hong Du; Tingting Xiang; Bingxue Lan; Sixi Wei; Hongyu Li; Hai Huang

doi:10.1016/j.bbrc.2023.149188

Super-enhancer-associated EEPD1 facilitates EMT-mediated metastasis by regulating the PI3K/AKT/mTOR pathway in gastric cancer

Biochem Biophys Res Commun. 2023 Dec 31:689:149188. doi: 10.1016/j.bbrc.2023.149188. Epub 2023 Nov 7.

Authors

Yong Jin¹, Ying Xia², Hong Du³, Tingting Xiang⁴, Bingxue Lan³, Sixi Wei⁵, Hongyu Li³, Hai Huang⁶

Affiliations

¹ 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.
² 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.
³ Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China; School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, China.
⁴ School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, China.
⁵ Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
⁶ Center for Clinical Laboratories, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China; School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, 550004, China. Electronic address: huanghai828@gmc.edu.cn.

PMID: 37976838
DOI: 10.1016/j.bbrc.2023.149188

Abstract

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.

Keywords: EEPD1; EMT; Gastric cancer; Super enhancers.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Movement
Cell Proliferation / genetics
Endodeoxyribonucleases / genetics
Endonucleases / metabolism
Gene Expression Regulation, Neoplastic
Humans
Phosphatidylinositol 3-Kinases / metabolism
Phosphoric Monoester Hydrolases / metabolism
Proto-Oncogene Proteins c-akt* / metabolism
Signal Transduction
Stomach Neoplasms* / pathology
TOR Serine-Threonine Kinases / metabolism

Substances

EEPD1 protein, human
Endodeoxyribonucleases
Endonucleases
Phosphatidylinositol 3-Kinases
Phosphoric Monoester Hydrolases
Proto-Oncogene Proteins c-akt
TOR Serine-Threonine Kinases
MTOR protein, human