SLC3A2 inhibits ferroptosis in laryngeal carcinoma via mTOR pathway.

Fangxing Wu, Gaoyun Xiong, Zejun Chen, Chenyang Lei, Qianqian Liu, Yundan Bai

Hereditas 2022 Jan 20

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This study aimed to explore the mRNA and protein expression of SLC3A2 in laryngeal carcinoma cells and tissues, and functional regulatory mechanism of SLC3A2 in cell ferroptosis of laryngeal carcinoma. We chose the key gene-SLC3A2 of DEGs from TCGA by bioinformatics analysis, and then we constructed stable knockdown of SLC3A2 in laryngeal carcinoma cells. MTT assay and clonogenic assay were used to determine cell viability and cell growth, respectively. The mRNA and protein expression were determined by RT-qPCR and western blotting, respectively. Xenograft tumor model was used to determine the role of SLC3A2 in tumor growth. The results of limma analysis recovered that 92 genes were involved in both upregulated DEGs and high risk of poor prognosis, whereas 36 genes were involved in both downregulated DEGs and low risk of poor prognosis. Pathway enrichment analysis indicated that mTOR signaling pathway and ferroptosis exerted a role in regulating these intersection genes. Moreover, SLC3A2 is a key gene in ferroptosis in laryngeal carcinoma. SLC3A2 is highly expressed in laryngeal carcinoma tissues and cells. Patients with high SLC3A2 expression exerted poor survival. SLC3A2 deficiency inhibited cell proliferation and foci formation. Furthermore, knockdown of SLC3A2 expression induced the efficacy of ferroptosis and suppressed ferroptosis related proteins expression. Mechanically, SLC3A2 deficiency facilitated ferroptosis through upregulating the expression of mTOR and P70S6K, whereas inhibited p-mTOR and p-P70S6K expression in laryngeal carcinoma cells. SLC3A2 deficiency inhibited tumorigenesis in nude mice. Our study suggests that SLC3A2 negatively regulates ferroptosis through mTOR pathway in laryngeal carcinoma. © 2022. The Author(s).

Citation

Fangxing Wu, Gaoyun Xiong, Zejun Chen, Chenyang Lei, Qianqian Liu, Yundan Bai. SLC3A2 inhibits ferroptosis in laryngeal carcinoma via mTOR pathway. Hereditas. 2022 Jan 20;159(1):6