Super-enhancer-driven IRF2BP2 enhances ALK activity and promotes neuroblastoma cell proliferation.

BACKGROUND: Super-enhancers (SEs) typically govern the expression of critical oncogenes and play a fundamental role in the initiation and progression of cancer. Focusing on genes that are abnormally regulated by SE in cancer may be a new strategy for understanding pathogenesis. In the context of this investigation, we have identified a previously unreported SE-driven gene IRF2BP2 in neuroblastoma (NB). METHODS: The expression and prognostic value of IRF2BP2 were detected in public databases and clinical samples. The effect of IRF2BP2 on NB cell growth and apoptosis was evaluated through in vivo and in vitro functional loss experiments. The molecular mechanism of IRF2BP2 was investigated by the study of chromatin regulatory regions and transcriptome sequencing. RESULTS: The sustained high expression of IRF2BP2 results from the activation of a novel SE established by NB master transcription factors MYCN, MEIS2 and HAND2, and they form a new complex that regulates the gene network associated with the proliferation of NB cell populations. We also observed a significant enrichment of the AP-1 family at the binding sites of IRF2BP2. Remarkably, within NB cells, AP-1 plays a pivotal role in shaping the chromatin accessibility landscape, thereby exposing the binding site for IRF2BP2. This orchestrated action enables AP-1 and IRF2BP2 to collaboratively stimulate the expression of the NB susceptibility gene ALK, thereby upholding the highly proliferative phenotype characteristic of NB. CONCLUSION: Our findings indicate that SE-driven IRF2BP2 can bind to AP-1 to maintain the survival of tumor cells via regulating chromatin accessibility of NB susceptibility gene ALK.

Ultrasound microbubble contrast agents: application to therapy for peripheral vascular disease.

Ultrasound contrast agents are not only effective in ultrasonic imaging but are also important tools for drug or gene delivery. Ultrasound beams can disrupt microbubbles and cell membranes, offering the opportunity to locally deliver drugs or genes. Liposome-shelled microbubbles have many advantages and are widely used in many applications, while Lipofectamine (Invitrogen, Life Technologies, Carlsbad, CA, USA), as a material of microbubble membranes, has been used to enhance the effects of gene delivery. Ultrasound contrast agents that have therapeutic effects can be used for treating peripheral vascular diseases, particularly in thrombotic and angiogenic diseases. A combination of targeted contrast agent and drug-carrying contrast agent may be safer and more effective in treating thrombosis. Vascular endothelial growth factor-loaded microbubbles are expected to treat a variety of neovascular diseases such as severe limb ischemia and other diseases. Although there are several limitations in the application of therapeutic ultrasound microbubble contrast agents, it will offer a new hope for the treatment of peripheral vascular disease.