AFF4 (AF4/FMR2 Family Member 4)

AFF4 drives metabolic reprogramming, tumor progression, and cisplatin resistance through PTEN-mediated activation of the PI3K/AKT/mTOR signaling pathway, highlighting AFF4 inhibition as a potential therapeutic strategy in LUAD.

METTL3 promotes chemoresistance (e.g. circ0008399/WTAP/TNFAIP3) and immune evasion (PD-L1 stabilization), while its overexpression correlates with poor prognosis and cisplatin resistance. By integrating METTL3's interactions with m6 A readers (YTHDF1/2, IGF2BP3) and erasers (ALKBH5), we propose targeting METTL3 as a strategy to enhance chemotherapy and immunotherapy efficacy. This work underscores METTL3's potential as a diagnostic biomarker and therapeutic target, advancing precision oncology in BC.

In conclusion,cinobufagin regulated microRNA-149-3p/AFF4 axis to inhibit proliferation of ovarian cancer cells and promote cell apoptosis. Targeting the microRNA-149-3p/AFF4 axis with cinobufagin could represent a novel therapeutic strategy for ovarian cancer.

In addition, AFF4 knockdown partially counteracted the effect of FENDRR on malignant phenotypes of BC cells. In summary, FENDRR represses BC cell proliferation, migration, invasion, stemness, and EMT process by targeting the miR-18a-5p/AFF4 axis.

The m6A-modified CircCDK14 binding to miR-93-5p played an important role in the osteogenesis of LF cells by targeting AFF4, providing a promising therapeutic target for OLF.

Intraperitoneal administration of PLGA resulted in dose-dependent and longer-lasting immune tolerance than subcutaneous administration. The induction of immune tolerance using PLGA may represent a future therapeutic option for patients with MOGAD.

The patient showed resistance to Tagraxofusp and Venetoclax, and he died about 16 months after diagnosis. Considering the predicted effect of the AFF4::IRF1 fusion on IRF1's antitumor effects and immune regulation, and the possibility of its relevance to the aggressive course observed in this case, we propose further evaluation of the clinical significance of this fusion in BPDCN in future cooperative group studies and the consideration of therapeutic strategies aimed at restoring IRF1-dependent antineoplastic effects in such cases.

Drug sensitivity analysis indicated that dasatinib, docetaxel, lapatinib, methotrexate, paclitaxel, and sunitinib may have better efficacy in the low-risk group. Finally, Immunohistochemistry (IHC) validated the expression of prognostic genes, demonstrating higher levels in tumor tissue compared to normal tissue. Our study has developed an effective disulfidptosis-related prognostic prediction tool for BC and provides personalized guidance for the clinical management and immunotherapy selection of BC patients.

The biological function of AFF4 is largely achieved through SEC assembly, regulates SRY-box transcription factor 2 (SOX2), MYC, estrogen receptor alpha (ESR1), inhibitor of differentiation 1 (ID1), c-Jun and noncanonical nuclear factor-κB (NF-κB) transcription and combines with fusion in sarcoma (FUS), unique regulatory cyclins (CycT1), or mixed lineage leukemia (MLL). We explore the prospects of using AFF4 as a therapeutic in Acquired immunodeficiency syndrome (AIDS) and malignant tumors and its potential as a stemness regulator.

Mechanistically, AFF4 promotes pause release likely by facilitating the binding of P-TEFb to Pol II. These results suggest that extent of the impact of AFF4 on pause release is likely to be context-dependent or cell-type dependent.

Finally, we obtained the positive correlation between c-Myc and AFF4 or AFF4 and HPRT1/IMPDH2 in clinical PDAC samples. Otherwise, we conducted data-mining and found that the expression levels of AFF4 and HPRT1/IMPDH2 are correlated with patients' prognosis, establishing AFF4 as a potential biomarker and therapeutic target for PDAC.

A combination screen reveals SEC inhibition synergistically potentiates the therapeutic efficacies of FDA-approved BCL-2 antagonist ABT-199, in part due to suppression of MCL1 expression, both in MYCN-amplified neuroblastoma cells and in patient-derived xenografts. These findings identify disruption of the MYCN-SEC regulatory axis as a promising therapeutic strategy in neuroblastoma.