TMEM44-AS1 promotes esophageal squamous cell carcinoma progression by regulating the IGF2BP2-GPX4 axis in modulating ferroptosis

Ruotong Yang; Junhu Wan; Liwei Ma; Fuyou Zhou; Zhengwu Yang; Zhuofang Li; Mingyuan Zhang; Liang Ming

doi:10.1038/s41420-023-01727-0

TMEM44-AS1 promotes esophageal squamous cell carcinoma progression by regulating the IGF2BP2-GPX4 axis in modulating ferroptosis

Cell Death Discov. 2023 Dec 1;9(1):431. doi: 10.1038/s41420-023-01727-0.

Authors

Ruotong Yang^#^{1

2}, Junhu Wan^#^{1

2}, Liwei Ma^{1

2}, Fuyou Zhou³, Zhengwu Yang^{1

2}, Zhuofang Li^{1

2}, Mingyuan Zhang^{1

2}, Liang Ming^{4

5}

Affiliations

¹ Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
² Key Clinical Laboratory of Henan province, Zhengzhou, China.
³ Thoracic Department, Anyang Tumor Hospital, Henan Key Medical Laboratory of Precise Prevention and Treatment of Esophageal Cancer, Anyang, China.
⁴ Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. mingliang@zzu.edu.cn.
⁵ Key Clinical Laboratory of Henan province, Zhengzhou, China. mingliang@zzu.edu.cn.

^# Contributed equally.

Abstract

The long non-coding RNA (lncRNA) TMEM44-AS1 is a novel lncRNA whose pro-carcinogenic role in gastric cancer and glioma has been demonstrated. However, its function in esophageal squamous cell carcinoma (ESCC) is unknown. In this study, we identified that TMEM44-AS1 was highly expressed in ESCC tissues and cells. Functionally, TMEM44-AS1 promoted ESCC cell proliferation, invasion and metastasis in vitro and in vivo. TMEM44-AS1 inhibited ferroptosis in ESCC cells, and ferroptosis levels were significantly increased after knockdown of TMEM44-AS1. Mechanistically, TMEM44-AS1 was positively correlated with GPX4 expression, and TMEM44-AS1 could bind to the RNA-binding protein IGF2BP2 to enhance the stability of GPX4 mRNA, thereby affecting ferroptosis and regulating the malignant progression of ESCC. In summary, this study reveals the TMEM44-AS1-IGF2BP2-GPX4 axis could influence cancer progression in ESCC. TMEM44-AS1 can be used as a potential treatment target against ESCC.

Abstract

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