EFNA3 (Ephrin A3)

The effects of DDX1 overexpression on cell proliferation, apoptosis, and lenvatinib resistance were significantly blocked by Ephrin-A3 knockdown. Mechanistically, DDX1 promotes lenvatinib resistance in HCC by regulating Ephrin-A3 mRNA stability and activating the Wnt/β-catenin pathway.  The increased DDX1 expression in HCC cells promotes lenvatinib resistance via regulating Ephrin-A3 mRNA stability and activating the Wnt/β-catenin pathway, indicating that targeting DDX1 may be an important strategy for overcoming lenvatinib resistance.

Functionally, EFNA3 promoted ACC cell proliferation and migration in vitro. The present study demonstrated that EFNA3 acts as an oncogene in ACC and may contribute to tumor aggressiveness via β-catenin activation and glycolytic reprogramming, and thus may serve as a potential biomarker for prognosis, immunotherapy sensitivity and drug repurposing, particularly involving statins.

Our findings suggest that EFNA3 promotes CRC metastasis, and that EphA3/EFNA3 signalling may promote EMT by activating the ERK signalling. These results indicate that the EphA3/EFNA3 axis could be a potential target for metastatic CRC.

Moreover, the cis interaction interferes with ligand binding in trans , attenuates EphA2 canonical signaling. Our results uncover a new mechanism of EphA2 regulation by its co-expressed ligand ephrin-A1 with important implications in its known roles in oncogenesis as well as other disease processes including development of cataract.

Silencing of NSUN5 decelerates LIHC progression by inhibiting glycolysis mediated by EFNA3 with m5C modification, highlighting the potential of NSUN5 as a therapeutic target for LIHC.

NGEF facilitates the infiltration of nerve and the growth of cancer cells in lung adenocarcinoma through the Ephrin-A3/EphA2 pathway, suggesting that NGEF is a promising target for disrupting interactions between nerves and tumors. Biomaterials that focus on NGEF are anticipated to be a potential treatment option for lung cancer.

We developed a novel HCC prognostic model utilizing SERGs, indicating that patients with high-risk score not only face a poorer prognosis but also may exhibit a diminished therapeutic response to immune checkpoint inhibitors (ICIs). This model is designed to tailor personalized treatment strategies to the individual needs of each patient, thereby improving the overall clinical outcomes for HCC patients. Furthermore, CBX2 is a promising candidate for therapeutic intervention in HCC.

hMAGEA2 promotes prostate cancer growth, metastasis, and tumorigenesis by regulating the EFNA3-Erk1/2 signaling pathway, indicating its potential as a therapeutic marker for prostate cancer.

EFNA3 could be a valuable prognostic factor in CM.

A reduction in the expression of these genes was seen in patients who achieved pathological complete response and/or major pathological response (N=27) (EFNA1: log2FC -0.92, p=0.01; EFNA3: log2FC -1.53, p=0.0005; EFNA4: log2FC -0.75, p=0.01; EPHA1: log2FC -1.77, p<0.00001) but not amongst patients who relapsed following cystectomy (N=17). Patients with high expression levels of EFNA1 (p = 0.03) and EFNA4 (p = 0.03) post-atezolizumab had a shorter relapse-free survival than those with low expression levels.ConclusionThese findings suggest that EFNA-EPHA signalling is associated with treatment resistance to PD-L1 inhibitor therapy in muscle-invasive urothelial carcinoma, therefore representing a potential biomarker and treatment target.

Necroptosis appears to play a critical role in the development of gastric cancer, prognosis and shaping of its tumor immune microenvironment. NRGPI can be used as a promising prognostic biomarker to identify gastric cancer patients with a cold tumor immune microenvironment and poor prognosis who may response to selected molecular targeted therapy.

EphrinA3 expression was negatively correlated with prognosis of patients with LUAD. EphrinA3 promoted proliferation, migration, and invasion of LUAD cells. EphrinA3 enhanced the phosphorylation of ERK and AKT, and potentiates EMT and MMP expression in LUAD cells.