EGLN1 induces tumorigenesis and radioresistance in nasopharyngeal carcinoma by promoting ubiquitination of p53 in a hydroxylase-dependent manner

Abstract

Egl-9 Family Hypoxia Inducible Factor 1 (EGLN1) is a proline hydroxylase mediating degradation of hypoxia-inducible factor α (HIFα) through the ubiquitination system. Studies have indicated an essential role for EGLN1 in angiogenesis and tumorigenesis. However, there is no consensus on the regulation of EGLN1 and its mechanism of action on nasopharyngeal carcinoma (NPC). This study explored the association of the expression of EGLN1 with characteristics of NPC tumors and its underlying mechanism. We found that the expression of EGLN1 showed a positive correlation with tumor T classification and clinical staging of patients with NPC. EGLN1 could promote cell proliferation, invasion and migration, and even enhance the cancer stem cells (CSCs) prosperity and radioresistance of NPC cells. Mechanistically, EGLN1 facilitated degradation of tumor protein p53 through the ubiquitination system. This effect could be weakened in the presence of dimethyloxalylglycine (DMOG), suggesting that EGLN1 down-regulated p53 based on its hydroxylase activity. In conclusion, overexpression of EGLN1 promoted oncogenesis and induced a CSC-like phenotype in NPC cells, then enhancing the ability for radioresistance by interacting with p53 in a hydroxylase-dependent manner. Thus, EGLN1 might serve as a potential therapeutic target for NPC.

Understanding Hypoxia-Driven Tumorigenesis: The Interplay of HIF1A, DNA Methylation, and Prolyl Hydroxylases in Head and Neck Squamous Cell Carcinoma

“…Meanwhile, data regarding HNSCC are not conclusive. In nasopharyngeal carcinoma, contrary to our results, the level of IHC-stained EGLN1 was detected to be higher compared to that in normal tissues, with its expression correlating with larger tumor size [ 26 ]. Lukkuuaa et al found low expression levels of EGLN1 protein in normal tissues and well-differentiated head and neck tumors and correlated these data with favorable radiotherapy responses [ 27 ].…”

Aucan affects autophagy induced apoptosis of glioma cells via regulating EGLN1

“…EGLN1, EGLN2, and EGLN3 are major family members, and EGLN1 is generally considered to be the major HIF1 hydroxylase, EGLN2 and EGLN3 play a role in ovarian cancer by regulating HIF1 under certain conditions (14). It has been reported that EGLN1 is a novel therapeutic target for lung cancer (15) and can also induce the occurrence of nasopharyngeal carcinoma(16).…”