Regulation and dysregulation of microRNA - transcription factor axes in differentiation and neuroblastoma

Development is characterized by dynamic changes in gene expression as cells traverse genetic pathways and make lineage-specific commitments. Transcription factors, which drive gene expression, and microRNAs, the largest class of post-transcriptional regulators, often function together within the same genetic networks. These interactions frequently include direct regulation of one another and shared target genes, forming feedback and feedforward loops that fine-tune gene expression to establish and maintain cell identity. The interplay between transcriptional and post-transcriptional regulation is particularly extensive during development, where disruptions in gene expression programs can cause cells to become trapped in immature proliferative states that result in paediatric cancers. This review focuses on the intricate cross-regulation between transcription factors and microRNAs, highlighting their contributions to developmental cancers with a particular emphasis on neuroblastoma, the most prevalent extracranial solid tumour in children, which arises from the failure of neural crest-derived cells to properly differentiate during sympathoadrenal development.