Transgelin promotes ferroptosis to inhibit the malignant progression of esophageal squamous cell carcinoma

Int J Oncol. 2023 Jul;63(1):76. doi: 10.3892/ijo.2023.5524. Epub 2023 May 19.

Abstract

The aim of the present study was to examine the function of transgelin (TAGLN) and its underlying mechanism in the ferroptosis of esophageal squamous cell carcinoma (ESCC) cells. To meet this aim, the association between TAGLN expression and the prognosis of patients with ESCC was determined using tissue samples and clinical data. Gene Expression Omnibus databank and Gene Set Enrichment Analysis data were used to examine which genes were co‑expressed with TAGLN, as well as the influence of TAGLN on ESCC. Subsequently, Transwell chamber, wound healing, Cell Counting Kit‑8 viability and colony formation assays were performed to observe the effects of TAGLN on the migration, invasion, viability and proliferation of Eca‑109 and KYSE‑150 cells. The interaction between TAGLN and p53 in the regulation of ferroptosis was detected using reverse transcription‑quantitative PCR, co‑immunoprecipitation and fluorescence co‑localization assays, and a xenograft tumor model was established to examine the effect of TAGLN on tumor growth. The level of TAGLN expression in patients with ESCC was found to be low, compared with normal esophageal tissue, and a positive association was identified between the prognosis of ESCC and TAGLN expression. The expression of the ferroptosis marker protein, glutathione peroxidase 4, was found to be high, whereas that of acyl‑CoA synthetase long‑chain family member 4 was lower in patients with ESCC compared with expression levels in healthy patients. The overexpression of TAGLN resulted in a significant decrease in the invasive and proliferative capabilities of Eca‑109 and KYSE‑150 cells in vitro compared with the control group; in vivo, TAGLN overexpression was found to significantly decrease tumor size, volume and weight after one month of growth. In addition, the proliferation, migration and invasion of Eca‑109 cells in vivo was stimulated by the knockdown of TAGLN. The results of the transcriptome analysis further demonstrated that TAGLN was able to induce ferroptosis‑associated cell functions and pathways. Finally, TAGLN overexpression was found to promote ferroptosis in ESCC through its interaction with p53. Taken together, the findings of the present study suggested that the malignant development of ESCC may be inhibited by TAGLN through the manifestation of ferroptosis.

Keywords: TAGLN; esophageal squamous cell carcinomas; ferroptosis; tumor invasion; tumor migration.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Esophageal Neoplasms* / pathology
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Ferroptosis*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Tumor Suppressor Protein p53 / genetics

Substances

  • transgelin
  • Tumor Suppressor Protein p53

Grants and funding

The present study was financially supported by The National Natural Science Foundation of China (grant nos. 82000511, 82170558 and 81900487), Scientific and Technological Projects of Tianjin (grant no. 21JCQNJC01120), Health Science and Technology Project of Tianjin (grant no. TJWJ2021QN006), Scientific Research Project of Tianjin Education Commission (grant no. 2019KJ197), Tianjin Science and Technology Plan Project (grant no. 21JCQNJC00990), Health Commission of Shanxi Province Science and Technology Guiding Project (grant no. 2021XM40), Basic Research Program of Shanxi Provincial Science and Technology Department (grant no. 20210302123013) and Key Technology Research and Development Project of Jincheng Science and Technology Bureau (grant no. 20210118).