Research Paper Volume 14, Issue 9 pp 3887—3909
Ox-LDL-mediated ILF3 overexpression in gastric cancer progression by activating the PI3K/AKT/mTOR signaling pathway
- 1 Department of Gastrointestinal Surgery, General Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
- 2 The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
- 3 Department of Nursing Department, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
Received: October 10, 2021 Accepted: April 21, 2022 Published: May 4, 2022https://doi.org/10.18632/aging.204051
How to Cite
Copyright: © 2022 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: This study aimed to investigate the relationship of dyslipidemia and interleukin-enhancer binding factor 3 (ILF3) in gastric cancer, and provide insights into the potential application of statins as an agent to prevent and treat gastric cancer.
Methods: The expression levels of ILF3 in gastric cancer were examined with publicly available datasets such as TCGA, and western blotting and immunohistochemistry were performed to determine the expression of ILF3 in clinical specimens. The effects of ox-LDL on expression of ILF3 were further verified with western blot analyses. RNA sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA) pathway analyses were performed to reveal the potential downstream signaling pathway targets of ILF3. The effects of statins and ILF3 on PI3K/AKT/mTOR signaling pathway, cell proliferation, cell cycle, migration and invasion of gastric cancer cells were investigated with Edu assay, flow cytometry and transwell assay.
Results: Immunohistochemistry and western blot demonstrated that the positive expression rates of ILF3 in gastric cancer tissues were higher than adjacent mucosa tissues. The ox-LDL promoted the expression of ILF3 in a time-concentration-dependent manner. ILF3 promoted the proliferation, cell cycle, migration and invasion by activating the PI3K/AKT/mTOR signaling pathway. Statins inhibited the proliferation, cell cycle, migration and invasion of gastric cancer by inhibiting the expression of ILF3.
Conclusions: These findings demonstrate that ox-LDL promotes ILF3 overexpression to regulate gastric cancer progression by activating the PI3K/AKT/mTOR signaling pathway. Statins inhibits the expression of ILF3, which might be a new targeted therapy for gastric cancer.
AFP: alpha-fetoprotein; Akt: serine-threonine kinase; BP: biological processes; CA125: cancer antigen 125; CA19-9: cancer antigen 19-9; CA72-4: cancer antigen 72-4; CC: cellular components; CEA: carcinoembryonic antigen; DRBPs: double-stranded RNA-binding proteins; GSEA: Gene Set Enrichment Analysis; ILF3: Interleukin-enhancer binding factor 3; LDL: low-density lipoprotein; LDL-C: low-density lipoprotein cholesterol; MF: molecular functions; MMP2: matrix metalloproteinase 2; MMP9: matrix metalloproteinase 9; mTOR: mammalian target of rapamycin; ox-LDL: oxidized low-density lipoprotein; p-Akt: phosphorylated serine-threonine kinase; PCNA: proliferating cell nuclear antigen; PI3K: phosphatidylinositol 3 kinase; p-mTOR: phosphorylated mammalian target of rapamycin; p-PI3K: phosphorylated phosphatidylinositol 3 kinases; ROS: reactive oxygen species; TCGA: The Cancer Genome Atlas; GESA: Gene Set Enrichment Analysis.