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

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 co­expressed with TAGLN, as well as the influence of TAGLN on ESCC. Subsequently, Transwell chamber, wound healing, Cell Counting Kit­8 viability and colony formation assays were performed to observe the effects of TAGLN on the migration, invasion, viability and proliferation of Eca­109 and KYSE­150 cells. The interaction between TAGLN and p53 in the regulation of ferroptosis was detected using reverse transcription­quantitative PCR, co­immunoprecipitation and fluorescence co­localization 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 acyl­CoA synthetase long­chain 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 Eca­109 and KYSE­150 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 Eca­109 cells in vivo was stimulated by the knockdown of TAGLN. The results of the transcriptome analysis further demonstrated that TAGLN was able to induce ferroptosis­associated 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.

Corrigendum: Transgelin Inhibits the Malignant Progression of Esophageal Squamous Cell Carcinomas by Regulating Epithelial-Mesenchymal Transition.

[This corrects the article DOI: 10.3389/fonc.2021.709486.].

Transgelin Inhibits the Malignant Progression of Esophageal Squamous Cell Carcinomas by Regulating Epithelial-Mesenchymal Transition.

OBJECTIVE: This article investigates the role of Transgelin (TAGLN) in the epithelial-mesenchymal transition (EMT) of esophageal squamous cell carcinomas (ESCC) and its possible mechanism of inhibiting the invasion of these cancers. METHODS: Tissue specimens and clinical information of patients with ESCC were collected to analyze the relationship between Transgelin expression level and prognosis of patients with ESCC. Transgelin siRNA was used to knock down Transgelin expression. The expression of Transgelin in Eca-109 and KYSE-150 cells was overexpressed by Transgelin-overexpressing plasmid. The effects of Transgelin overexpression and knockdown on the proliferation of Eca-109 and KYSE-150 cells were examined by Transwell chamber, scratch assay, and CCK-8 cell activity assay. RT-PCR and Western blot were used to detect the effect of Transgelin overexpression or knockdown on the mRNA and protein expressions of E-cadherin and Vimentin. TCGA data were used to analyze Transgelin co-expressed genes and further study the GO and KEGG enrichment analysis results under the influence of Transgelin. RESULTS: The expression of Transgelin was low in ESCC, and its expression level was positively correlated with the prognosis of patients with ESCC. The targeted Transgelin siRNA and Transgelin-overexpressing plasmid can effectively regulate the expression of Transgelin mRNA and protein in Eca-109 and KYSE-150 cells. After overexpression of Transgelin, the invasion and proliferation abilities of Eca-109 and KYSE-150 cells were significantly decreased compared with those of the control group (P < 0.05). However, Transgelin knockdown could promote the proliferation, migration, and invasion of ESCC cells. The overexpression of Transgelin inhibits EMT in ESCC. With the increase of Transgelin expression in Eca-109 and KYSE-150 cells, the expression of E-cadherin increased, while the expression of Vimentin decreased, and the difference was statistically significant (P < 0.05). CONCLUSION: Transgelin can inhibit the malignant progression of ESCC by inhibiting the occurrence of EMT.