95% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Genet.
Sec. Cancer Genetics and Oncogenomics
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1549371
RNA-seq analysis reveals key genes associated with downregulation of APE1 in esophageal squamous cell carcinoma
Provisionally accepted- Department of Radiation Oncology, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
Objective: This study aims to explore the impact of APE1 gene knockout on the transcriptome of esophageal cancer cells and conduct a preliminary screening of APE1-regulated target genes to provide a basis for understanding APE1 target genes and finding new anti-esophageal cancer therapeutic targets.Methods: We collected 100 patients with esophageal squamous cell carcinoma (ESCC), analyzed the expression of APE1 in ESCC by immunohistochemical, and analyzed the overall survival. TE-1 cells with APE1 knockout were used for transcriptome sequencing (RNA sequencing, RNA-Seq) detection, and GO and KEGG enrichment analysis of differentially expressed genes was conducted. Proteinprotein interaction (PPI) network analysis was performed on the genes in the intersection of differential genes between the two sequencing datasets. The qRT-PCR and Western blotting experiments were employed to confirm the effect of APE1 knockdown on the expression levels of FN1, TNF, and IL-6 in esophageal cancer cells.Results: APE1 highly expressed in ESCC tissue, and its high expression leads the worse OS. The stable transfected TE-1 cell line with knockdown of the APE1 gene was successfully constructed, with a 设置了格式: 西班牙语(西班牙) knockdown efficiency of 100%. RNA-seq analysis revealed that 2060 differential genes were detected between sh-APE1APE1-KO stably transfected cells and their corresponding sh-NCAPE1-YD cells, with 1063 upregulated genes and 997 downregulated genes. RNA-seq analysis found that differentially expressed genes after APE1 knockout in TE-1 cells were primarily enriched in pathways related to metabolism, extracellular matrix, inflammatory response, and angiogenesis. PPI network analysis demonstrated that FN1, TNF, and IL-6 may be essential target genes of APE1. The three core genes of FN1, TNF, and IL-6 were confirmed using qRT-PCR and Western blotting, and the results were consistent with the transcriptome sequencing results.Conclusion: Knocking out APE1 can affect the function, related pathways, and downstream target gene expression of ESCC cells. APE1 can promote the transcriptional expressions of FN1 and IL6 genes while inhibiting the TNF gene. FN1, TNF, and IL-6 may be potential target genes regulated by APE1 in esophageal cancer.
Keywords: RNA-Seq, Ape1, esophageal cancer, molecular target, bioinformatics
Received: 21 Dec 2024; Accepted: 03 Apr 2025.
Copyright: © 2025 Chu, Liu, Liu, Li, Song, Gan, Wang, Liu and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zongwen Liu, Department of Radiation Oncology, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
Chen Sun, Department of Radiation Oncology, Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.