Research Paper Volume 13, Issue 10 pp 13626—13643
E2F2 inhibition induces autophagy via the PI3K/Akt/mTOR pathway in gastric cancer
- 1 Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
- 2 Department of Oncology, Qingdao Women and Children’s Hospital, Qingdao, Shandong, China
- 3 Department of Emergency Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
- 4 Central Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
Received: November 24, 2020 Accepted: March 14, 2021 Published: April 21, 2021
https://doi.org/10.18632/aging.202891How to Cite
Copyright: © 2021 Li 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.
Abstract
Background: E2F2 is a member of the E2F transcription factor family and has important but not fully understood biological functions in cancers. The biological role of E2F2 in gastric cancer (GC) also remains unclear.
Methods: We examined the expression levels of E2F2 in GC using publicly available datasets such as TIMER, Oncomine, GEPIA, UALCAN, etc., and in our patient cohort, using quantitative real-time PCR, western blotting, and immunohistochemistry. We further investigated the effects of E2F2 on phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling, autophagy, and the migration and invasion of GC cells by the wound healing assay, Transwell assay and transmission electron microscopy.
Results: E2F2 was highly expressed in both GC tissues and cells compared with normal gastric tissues/cells. High E2F2 expression was associated with poor overall survival (OS). In addition, the expression of E2F2 in GC was strongly correlated with a variety of immune markers. E2F2 overexpression promoted the migration and invasiveness of GC cells in vitro through inhibition of PI3K/Akt/mTOR-mediated autophagy.
Conclusion: High E2F2 expression was associated with the characteristics of invasive tumors and poor prognosis. E2F2 also had potential modulatory effects on tumor immunity. We discovered a novel function of E2F2 in the regulation of PI3K/Akt/mTOR-mediated autophagy and the downstream processes of cell migration and invasion.
Abbreviations
GC: gastric cancer; TIMER: Tumor Immune Estimation Resource; DAVID: Database for Annotation, Visualization, and Integrated Discovery; OS: overall survival; PI3K: phosphoinositide-3 kinase; mTOR: mammalian target of rapamycin; TCGA: The Cancer Genome Atlas; GEPIA: Gene Expression Profiling Interactive Analysis; GO: gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; BPs: biological processes; CC: cell composition; MF: molecular function; TMAs: tissue microarrays; IHC: immunohistochemistry; FBS: fetal bovine serum; qPCR: real-time quantitative PCR; PBS: phosphate-buffered saline; CNV: copy number variation.