Nazki Fakhira H, Bracken Cameron P
Laboratory Head - Gene Regulatory Networks Laboratory, Centre for Cancer Biology, University of South Australia, Bradley Building, Rm HB-9-31, North Terrace, Adelaide, South Australia, 5000, Australia.
School of Biological Sciences, Faculty of Sciences, University of Adelaide, Adelaide, SA, Australia.
Cell Mol Life Sci. 2025 Aug 8;82(1):304. doi: 10.1007/s00018-025-05832-4.
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.
发育的特征是随着细胞穿越遗传途径并做出谱系特异性的分化,基因表达会发生动态变化。驱动基因表达的转录因子和最大的一类转录后调节因子——微小RNA,通常在相同的遗传网络中共同发挥作用。这些相互作用常常包括相互之间的直接调控以及共享的靶基因,形成反馈和前馈回路,对基因表达进行微调以建立和维持细胞身份。转录调控和转录后调控之间的相互作用在发育过程中尤为广泛,在这个过程中,基因表达程序的破坏会导致细胞被困在不成熟的增殖状态,从而引发儿童癌症。本综述聚焦于转录因子和微小RNA之间复杂的交叉调控,强调它们对发育性癌症的影响,特别着重于神经母细胞瘤,这是儿童中最常见的颅外实体瘤,它是由于神经嵴衍生细胞在交感肾上腺发育过程中未能正常分化而产生的。