EDDM3A drives gastric cancer progression by promoting HIF-1\u03b1-dependent aerobic glycolysis

Tao Wu,Bo Zhang,Nan Wang,Guo-Zhan Jia,Jia-Xing He,Shi-Qi Liu,Xian-Li He,Zhan-Sheng Zhang,Shuai Zhou,Ying Yang

doi:10.1038/s41389-022-00379-6

Tao Wu, Bo Zhang + Show 8 more

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https://doi.org/10.1038/s41389-022-00379-6

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Journal: Oncogenesis	Publication Date: Jan 17, 2022
Citations: 2	License type: open-access

Affiliation: Tang Du Hospital, Air Force Medical University

Abstract

Epididymal protein 3A (EDDM3A) is a protein involved in sperm maturation. It has been demonstrated that EDDM3A expression is upregulated and promotes cell proliferation in non-small cell lung cancer (NSCLC). However, the role of EDDM3A in other types of human cancers, including gastric cancer (GC), is still unexplored. Here, we show that the expression of EDDM3A is significantly upregulated in gastric cancer (GC) tissues and its upregulation correlates with poorer survival in patients with gastric cancer. Knockdown of EDDM3A inhibited growth and metastasis of GC cells, whereas overexpression of EDDM3A exhibited the opposite effect. Mechanistically, enhanced aerobic glycolysis mediated by upregulation of HIF-1α and subsequently increased target glycolytic genes and decreased mitochondrial biogenesis was found to contribute to the promotion of tumor growth and metastasis by EDDM3A in GC cells. Additionally, upregulation of EDDM3A in GC is at least partially mediated by downregulation of miR-618. In conclusion, elevated EDDM3A plays a pivotal oncogenic role in gastric carcinogenesis, suggesting it as a potential therapeutic target for treatment of GC.

Highlights

Gastric cancer (GC) is one of the fifth most common malignancies and the third leading cause of cancer-related mortality worldwide
Epididymal protein 3A (EDDM3A) expression is increased in gastric cancer (GC) and inversely associated with patient survival To explore the roles of EDDM3A in GC, we first determined its expression in 30 GC tissues and paired adjacent non-tumor tissues using quantitative real-time PCR (qRT-PCR) analysis
We found that GC patients with high expression of EDDM3A had significant poorer overall and recurrence-free survival than those with low EDDM3A expression (Fig. 1E, F)

Summary

Introduction

Gastric cancer (GC) is one of the fifth most common malignancies and the third leading cause of cancer-related mortality worldwide. Despite several advances in the management of GC, the effective therapies for GC and long-term survival of patients remain poor, mainly due to the poor understanding of novel causative molecular leading to malignant transformation [3, 4]. It is extremely urgent to further explore the molecular mechanisms that regulate GC and to develop the novel therapies. Epididymal protein 3A (EDDM3A) gene is located on human chromosome (chr) 14q11.2, which encodes a protein involved in the maturation of sperm [5]. The role of EDDM3A in other types of human cancers, especially the underlying mechanism still unexplored, including gastric cancer (GC)

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