High expression of DARS2 indicates poor prognosis in lung adenocarcinoma

J Clin Lab Anal. 2022 Oct;36(10):e24691. doi: 10.1002/jcla.24691. Epub 2022 Sep 9.

Abstract

Background: DARS2 was overexpressed in multiple tumor types, but the biological role of DARS2 in lung adenocarcinoma (LUAD) have not been elucidated.

Methods: Firstly, the DARS2 expression in LUAD was explored using The Cancer Genome Atlas (TCGA). Then, qRT-PCR and Western blot were performed to confirm DARS2 expression in LUAD. Next, Cox regression and Kaplan-Meier methods were utilized to evaluate whether DARS2 expression can affect the overall survival. The relationships between DARS2 expression and clinicopathological characteristics were investigated by TCGA database. Moreover, we utilized Gene Set Enrichment Analysis (GSEA) to detect DARS2-related signaling pathways in LUAD. Finally, the special function of DARS2 in cell proliferation, invasion and apoptosis was assessed in vitro.

Results: The higher expression of DARS2 was found in LUAD compared to para-carcinoma tissues and significantly related to tumor stage, T stage, and M stage. The survival analysis indicated that DARS2 overexpression was related to poor prognosis in LUAD. Multivariate analysis suggested that DARS2 expression was a prognostic indicator. GSEA revealed that DARS2 was primarily involved in cell cycle-related pathways. In addition, upregulation of DARS2 facilitated LUAD cell proliferation, migration, invasion and inhabited apoptosis, DARS2 knockdown showed an opposite result.

Conclusion: DARS2 modulates the proliferation, invasion and apoptosis of LUAD cells, and sever as a promising therapeutic target for LUAD.

Keywords: DARS2; apoptosis; lung adenocarcinoma; prognosis; tumorigenesis.

MeSH terms

  • Adenocarcinoma of Lung* / pathology
  • Aspartate-tRNA Ligase* / genetics
  • Aspartate-tRNA Ligase* / metabolism
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms* / pathology
  • Prognosis

Substances

  • Aspartate-tRNA Ligase
  • DARS2 protein, human