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Research Paper|Volume 16, Issue 4|pp 3934—3954

Functional enrichment analysis reveals the involvement of DARS2 in multiple biological pathways and its potential as a therapeutic target in esophageal carcinoma

Xu-Sheng Liu1, Zi-Yue Liu1, Dao-Bing Zeng1, Jian Hu2, Xuan-Long Chen3, Jiao-Long Gu4, Yan Gao1, Zhi-Jun Pei1
  • 1Department of Nuclear Medicine, Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China
  • 2Department of Critical Care Medicine, Danjiangkou First Hospital, Danjiangkou 420381, Hubei, China
  • 3Department of Medical Ultrasound, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China
  • 4Department of Obstetrics and Gynecology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China
* Equal contribution
Received: October 6, 2023Accepted: January 17, 2024Published: February 20, 2024
https://doi.org/10.18632/aging.205569

Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Objective: The enzyme Aspartyl tRNA synthetase 2 (DARS2) is a crucial enzyme in the mitochondrial tRNA synthesis pathway, playing a critical role in maintaining normal mitochondrial function and protein synthesis. However, the role of DARS2 in ESCA is unclear.

Materials and methods: Transcriptional data of pan-cancer and ESCA were downloaded from UCSC XENA, TCGA, and GEO databases to analyze the differential expression of DARS2 between tumor samples and normal samples, and its correlation with clinicopathological features of ESCA patients. R was used for GO, KEGG, and GSEA functional enrichment analysis of DARS2 co-expression and to analyze the connection of DARS2 with glycolysis and m6A-related genes. In vitro experiments were performed to assess the effects of interfering with DARS2 expression on ESCA cells. TarBase v.8, mirDIP, miRTarBase, ENCORI, and miRNet databases were used to analyze and construct a ceRNA network containing DARS2.

Results: DARS2 was overexpressed in various types of tumors. In vitro experiments confirmed that interfering with DARS2 expression significantly affected the proliferation, migration, apoptosis, cell cycle, and glycolysis of ESCA cells. DARS2 may be involved in multiple biological pathways related to tumor development. Furthermore, correlation and differential analysis revealed that DARS2 may regulate ESCA m6A modification through its interaction with METTL3 and YTHDF1. A ceRNA network containing DARS2, DLEU2/has-miR-30a-5p/DARS2, was successfully predicted and constructed.

Conclusions: Our findings reveal the upregulation of DARS2 in ESCA and its association with clinical features, glycolysis pathway, m6A modification, and ceRNA network. These discoveries provide valuable insights into the molecular mechanisms underlying ESCA.