Cell Death Dis: ZNF750 downsetting activates DANCR/miR-4707-3p/FOXC2 pathway promotes angiogenesis of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies in esophageal cancer, with more than 477,900 new cases and 375,000 deaths each year in ChinaAlthough chemotherapy and radiation therapy can improve the prognosis of the disease, the recurrence rate of the disease is high, and the five-year survival rate of the disease is only 20% due to the combination of treatment options and limited research on related molecular markersrecent studies analyzed genomic changes in ESCC and identified related significant mutant genes (SMGs), including TP53, ZNF750, NOTCH, FAT1, NFE2L2 gene mutations, SOX2, TERT, FGFR1, MDM1 gene copy increase, and common deletion of RB1 geneAmong these genes, ZNF750 is a cytonuclear factor that plays a key role in the programming process of end-of-epidermal differentiation regulated by genesHowever, its clinical relevance and potential molecular mechanisms are still to be studiedin this study, the researchers revealed the relationship between ZNF750 mutation and the corresponding clinical pathological characteristics and its prognosis effect sand, and further studied the function and potential mechanism of ZNF750 in angiogenesisthe researchers found a significant correlation between mutations or deletions of ZNF750 and the degree of malignancy and adverse prognosis in ESCC patientsIn ESCC cells, a decrease in the level of Expression of ZNF750 leads to increased angiogenesis in the human umbilical venous endothelial cells (HUVEC) and the human arterial endothelial cells (HAEC), which may be regulated indirectly by FOXC2The results of RNA-seq and ChIP experiments show that lncRNA DANCR is a direct downstream target for ZNF750In addition, the expression of tapping low ZNF750 induces the expression of DANCR, while the expression of DANCR can prevent miR-4707-3p from interacting with FOXC2 in ceRNA form and acting as its microRNA molecular sponge, resulting in enhanced FOXC2 signal transduction pathways and angiogenesis capabilitiesConversely, expressing ZNF750 reverses that effect, the study revealed a new mechanism for ZNF750, which can be used as an important biomarker for esophageal squamous cell carcinoma metastasis and prognosis, and provides a potential therapeutic target for patients with esophageal squamous cell carcinoma with ZNF750 mutation