N4BP2L2 (NEDD4 Binding Protein 2 Like 2)

Although published accuracies are encouraging, the majority of studies have small cohorts and lack external validation, and preanalytical handling and reporting heterogeneity are significant. Thus, strong standardization and regulatory level validation are necessary for circRNA testing to be established as a routine EOC diagnosis, risk stratification, or treatment monitoring tool.

Functional assays in both T47D and MCF7 cells demonstrated that co-expression of N4BP2L2 restored HR activity and reduced olaparib sensitivity in EXO1-overexpressing cells. These findings suggest EXO1 overexpression serves as a marker of functional HR deficiency and a potential predictor of PARP inhibitor response, highlighting the EXO1-N4BP2L2 axis as a promising biomarker and therapeutic target, especially for guiding PARP inhibitor use beyond BRCA-mutated tumors.

The AID model is a promising biomarker for accurately determining survival and predicting the effectiveness of immunotherapy in STAD patients. GLS1 plays a crucial role in driving tumor proliferation and migration and may act as a potential tumor biomarker of STAD.

Finally, tumorigenicity assay demonstrated that circ-N4BP2L2 facilitated NSCLC tumor growth in vivo. Taken together, circ-N4BP2L2 enhanced NSCLC progression via the miR-135a-5p/ARL5B axis, which may provide a novel therapeutic target of NSCLC.

Furthermore, inhibition of miR-340-5p reversed the anti-cancer effects of circN4BP2L2 or CXCR4 silencing. Our data indicated an oncogenic role of circN4BP2L2 in CRC via regulation of the miR-340-5p/CXCR4 axis, which may be a promising biomarker and target for CRC treatment.

CircN4BP2L2 might serve as a promising diagnostic biomarker for both type I and type II EOC. The diagnostic safety for circN4BP2L2 in early-stage type I or type II EOC is also acceptable. Further large-scale well-designed studies are warranted to investigate whether circN4BP2L2 is specific for all histologic subgroups.

Moreover, in vivo experiments showed that depletion of cricN4BP2L2 suppressed CRC tumorigenesis growth. In conclusion, CAFs-exo cricN4BP2L2 promoted the CRC cells stemness and oxaliplatin resistance through EIF4A3/PI3K/AKT/mTOR pathway.