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

Chen,Qiuyu; Zhang,Lingyun; Wan,Changshan; Yang,Boli; Kong,Xiangxu; Xu,Xin; Gu,Yu; Wang,Chen; Liu,Xiaotong; Ding,Qian; Zhu,Lanping; Li,Ying; Wang,Bangmao; Zhong,Weilong

doi:10.3892/ijo.2023.5524

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

Authors:
- Qiuyu Chen
- Lingyun Zhang
- Changshan Wan
- Boli Yang
- Xiangxu Kong
- Xin Xu
- Yu Gu
- Chen Wang
- Xiaotong Liu
- Qian Ding
- Lanping Zhu
- Ying Li
- Bangmao Wang
- Weilong Zhong
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Affiliations: Department of Gastroenterology and Hepatology, Tianjin Medical University General Hospital, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, P.R. China, Department of Pathology, General Hospital of Jincheng, Jincheng, Shanxi 048006, P.R. China
Published online on: May 19, 2023 https://doi.org/10.3892/ijo.2023.5524
Article Number: 76
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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