EPS15-AS1 Inhibits AKR1B1 Expression to Enhance Ferroptosis in Hepatocellular Carcinoma Cells

Man, Quan; Zhang, Guoyou; Chen, Xiaojun; Na, Sa Ren; Bai, Siguleng; Zhi, Haoqiang; Sun, Ling; Pang, Huifang

doi:10.7150/jca.89993

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J Cancer 2024; 15(4):1030-1040. doi:10.7150/jca.89993 This issue Cite

Research Paper

EPS15-AS1 Inhibits AKR1B1 Expression to Enhance Ferroptosis in Hepatocellular Carcinoma Cells

Quan Man¹, Guoyou Zhang¹, Xiaojun Chen², Sa Ren Na³, Siguleng Bai¹, Haoqiang Zhi², Ling Sun², Huifang Pang^2,✉

1. General Surgery, Tongliao City Hospital, Tongliao, Inner Mongolia, 028000, China.
2. Department of Gastroenterology, Tongliao City Hospital, Tongliao, Inner Mongolia, 028000, China.
3. Department of Pathology, Tongliao City Hospital, Tongliao, Inner Mongolia, 028000, China.

Citation:

Man Q, Zhang G, Chen X, Na SR, Bai S, Zhi H, Sun L, Pang H. EPS15-AS1 Inhibits AKR1B1 Expression to Enhance Ferroptosis in Hepatocellular Carcinoma Cells. J Cancer 2024; 15(4):1030-1040. doi:10.7150/jca.89993. https://www.jcancer.org/v15p1030.htm

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Abstract

Epidermal growth factor receptor substrate 15 (EPS15) is part of the EGFR pathway and has been implicated in various tumorigenesis. Increasing evidence suggests that long noncoding RNA (lncRNA) plays an essential role in liver hepatocellular carcinoma (LIHC) by regulating the expression of proteins and genes. Through analysis of the cancer genome atlas (TCGA) database, we found that EPS15 is highly expressed in LIHC tissue, and lncRNA EPS15-antisense1 (EPS15-AS1) decreased in LIHC cell lines. However, the function of EPS15-AS1 in LIHC is still unknown. When EPS15-AS1 was overexpressed in HepG2 cell lines, the expression of EPS15 was reduced and cell activity and invasiveness were inhibited. In addition, we observed an increase in Fe²⁺ ion and lipid peroxidation after overexpression of EPS15-AS1, and further analysis showed that the susceptibility to ferroptosis increased. Aldo-keto reductase family 1 member B 1 (AKR1B1) belongs to the aldo/keto reductase superfamily and is involved in maintaining the cellular redox balance. Survival analysis revealed that patients with a higher level of AKR1B1 have a lower survival rate in the TCGA database. We also found that EPS15 enhanced the AKR1B1 expression in LIHC, and AKR1B1 had the ability to promote cell invasiveness. Moreover, overexpression of AKR1B1 alleviated the promoting effect of EPS15-AS1 on ferroptosis. Therefore, EPS15-AS1 can induce ferroptosis in hepatocellular carcinoma cells by inhibiting the expression of EPS15 and AKR1B1 and disrupting the redox balance. EPS15 and AKR1B1 may serve as biomarkers for diagnosis and lncRNA EPS15-AS1 potential drug for LIHC.

Keywords: EPS15-AS1, AKR1B1, hepatocellular carcinoma, ferroptosis

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APA

Man, Q., Zhang, G., Chen, X., Na, S.R., Bai, S., Zhi, H., Sun, L., Pang, H. (2024). EPS15-AS1 Inhibits AKR1B1 Expression to Enhance Ferroptosis in Hepatocellular Carcinoma Cells. Journal of Cancer, 15(4), 1030-1040. https://doi.org/10.7150/jca.89993.

ACS

Man, Q.; Zhang, G.; Chen, X.; Na, S.R.; Bai, S.; Zhi, H.; Sun, L.; Pang, H. EPS15-AS1 Inhibits AKR1B1 Expression to Enhance Ferroptosis in Hepatocellular Carcinoma Cells. J. Cancer 2024, 15 (4), 1030-1040. DOI: 10.7150/jca.89993.

NLM

CSE

Man Q, Zhang G, Chen X, Na SR, Bai S, Zhi H, Sun L, Pang H. 2024. EPS15-AS1 Inhibits AKR1B1 Expression to Enhance Ferroptosis in Hepatocellular Carcinoma Cells. J Cancer. 15(4):1030-1040.

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