EGLN1 (Egl-9 Family Hypoxia Inducible Factor 1)

So far, the activity of EGLN1/PHD2 has been characterized in different cell types, albeit with controversial outcomes in different cancer settings. This Review aims to discuss the role of EGLN1/PHD2 in the TME and the strategies targeting this protein that might be used to hit tumors.

This study systematically reveals the critical protective role of EGLN1 in high BMI-associated CRC and underscores its value as a potential drug target. EGLN1 influences CRC pathogenesis by modulating multiple dimensions, including the hypoxia response, energy metabolism, the immune microenvironment, and the gut microbiota. The natural compound Cianidanol, as a modulator of EGLN1, demonstrated significant anti-tumor activity in vitro. These findings provide new insights into the molecular mechanisms linking obesity and CRC and establish a theoretical foundation for developing precision therapeutic strategies targeting EGLN1.

Our findings support a potential causal relationship between the inhibition of EGLN1 and EGLN2 and the development of specific cancer types.

Finally, a combination of genetic and pharmacological stabilisation of HIF during neonatal heart injury led to prolonged epicardial activation, preservation of myocardium, augmented infarct resolution and preserved function beyond the 7-day regenerative window. These findings suggest modulation of HIF signalling extends epicardial activation to maintain myocardial survival beyond the neonatal regenerative window and may represent a viable strategy for treating ischaemic heart disease.

Notably, we identified one of the PHD2 mutants, P317R, to retain comparably wild-type capacity to hydroxylate the predominant proline in the C-terminal ODD but had uniquely compromised ability to hydroxylate the N-terminal ODD proline. These findings support the notion that deregulation of HIF ultimately underlies PHD2-driven erythrocytosis and challenge the currently held uncertainty that the N-terminal ODD prolyl-hydroxylation event is dispensable in normal hypoxic signaling pathway.

Taken together, our findings may contribute to the treatment and prognosis prediction of MM patients.

In summary, our findings position EGLN1 as a promising multi-faceted biomarker in CRC, with implications for prognosis, immune microenvironment modulation, and potential therapeutic targeting.

In this study, we identified circulating miRNAs differentially expressed between R-CHOP refractory and responding subjects by small-RNA sequencing on serum from 33 DLBCL patients...EGLN1 and TXNRD1, regulators of oxygen metabolism and redox homeostasis, were identified as miRNA targets and the silencing or inhibition of these genes impaired cell viability and induced ferroptosis. These results support the application of a two-miRNA signature and its targets for novel combined therapeutic interventions in DLBCL.

We have constructed an angiogenesis-related gene prognostic signature that enriches the prognostic assessment system for AML and provides novel therapeutic directions for this disease.

Seven efferocytosis-related prognostic genes were identified as prognostic markers for CESC, providing a scientific basis for further research on their role in disease progression.

This study provides new insights into EGLN biology and identifies EGLN1 as a potential biomarker for cervical cancer.

Inhibition of EGLN1 compromises tRCC cell growth by stabilizing HIF-1α and promoting metabolic reprogramming away from OXPHOS, thus representing a vulnerability for OXPHOS-dependent tRCC cells. Our study defines tRCC as being dependent on a mitochondria-centred metabolic programme driven by TFE3 fusions and nominates EGLN1 inhibition as a therapeutic strategy in this cancer.