Transgelin Inhibits the Malignant Progression of Esophageal Squamous Cell Carcinomas by Promotes Ferroptosis

Objective: This article aimed to investigate the role of Transgelin (TAGLN) in the ferroptosis of esophageal squamous cell carcinoma (ESCC) cells and its possible mechanism.Methods: Tissue specimens and clinical information of patients with ESCC were collected to analyze the relationship between TAGLN expression level and the prognosis of patients with ESCC. GEO databank and GSEA data were used to analyze TAGLN’s co-expressed genes and the influence of TAGLN on ESCC. The expression of TAGLN in Eca-109 and KYSE-150 cells was overexpressed by TAGLN-overexpressing plasmid. The effects of TAGLN overexpression on the proliferation of Eca-109 and KYSE-150 cells were examined by Transwell chamber, scratch assay, colony formation, and CCK-8 cell activity assay. TAGLN siRNA was used to knock down TAGLN expression. The effects of TAGLN overexpression and knockdown on the proliferation of Eca-109 cells in vivo were detected by qRT-PCR and Western blot. Transcriptome analysis results further demonstrated the GO and KEGG enrichment analysis results under the influence of TAGLN. STRING tool was used to analyze the PPI network of TAGLN protein, and analysis results showed that TP53 determined the interactions involved in the progression of ESCC. The effects of TAGLN overexpression on the occurrence of ferroptosis and the change of Ferroptosis marker proteins in Eca-109 and KYSE-150 cells were examined. The interaction of TAGLN with p53 in the regulation of ferroptosis was detected by qRT-PCR, Co-IP, and fluorescence co-localization assay.Results: The expression of TAGLN was low in ESCC, and its expression level was positively correlated with the prognosis of patients with ESCC. The expression of ferroptosis marker proteins GPX4 was high, whereas ACSL4 expression decreased in ESCC. After the overexpression of TAGLN, the invasion and proliferation abilities of Eca-109 and KYSE-150 cells in vitro and in vivo were significantly decreased compared with the control group (P < 0.05). However, TAGLN knockdown could promote the proliferation, migration, and invasion of Eca-109 cells in vivo. The results of transcriptome analysis further demonstrated that TAGLN can induce the ferroptosis relative cell functions and pathways. TAGLN overexpression can promote ferroptosis in ESCC by interacting with TP53.Conclusion: TAGLN can inhibit the malignant progression of ESCC by promoting the occurrence of ferroptosis.Funding Information: This study was supported by The National Natural Science Foundation of China (Grant nos. 82000511, 82170558, 81900487), Health Science and Technology Project of Tianjin (TJWJ2021QN006), Scientific Research Project of Tianjin Education Commission (2019KJ197), Zhao Yicheng Medical Science Foundation Youth Incubation Project of Tianjin (ZYYFY2019010), Tianjin Medical University General Hospital “Excellent Rising Star” Cultivation Project (209060400601), Health Commission of Shanxi Province Science and Technology Guiding Project (2021XM40), Basic Research Program of Shanxi Provincial Science and Technology Department (20210302123013), Key Technology Research and Development Project of Jincheng Science and Technology Bureau (20210118).Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: This research was conducted in accordance with the Helsinki Declaration of the World Medical Association. Every patient signed an informed consent form. The experiment was approved by the Ethics Committee of Tianjin Medical University General Hospital (Ethical NO. IRB2021-WZ-134).