Follicular-cell-derived thyroid cancers that progress from differentiated tumors to poorly differentiated or anaplastic states commonly lose thyroid lineage identity, radioiodine avidity, and favorable clinical behavior. Genetic and signaling alterations within tumor cells explain part of this transition, but they do not fully account for the coexistence of different differentiation states within the same molecular subtype or even within the same lesion. Increasing functional evidence indicates that dedifferentiation is maintained by reciprocal interactions between malignant cells and the immune, stromal, metabolic, and inflammatory microenvironment. Cancer-associated fibroblast glycolysis and lactate release, IL-6/CXCL8-driven inflammatory signaling, hypoxia, transforming growth factor-beta signaling, and tumor-associated macrophage feedback can suppress thyroid lineage programs while promoting plasticity, invasion, and treatment resistance. Here, we synthesize mechanistic studies supported by genetic perturbation, co-culture, pharmacologic blockade, iodine-uptake assays, animal models, or patient-level radioiodine endpoints. We distinguish functional dedifferentiation from epithelial–mesenchymal transition, stemness, and lymph-node metastasis, and discuss therapeutic strategies that combine tumor-cell redifferentiation with targeting of microenvironmental feedback to restore durable radioiodine sensitivity.
Qing Ye, Xiao-Ping Yu· International Journal of Mol...· 0 citations
Abstract Bacterial regulatory small RNAs (sRNAs) are integral components of posttranscriptional control, shaping environmental adaptation, metabolic homeostasis, and virulence. Advances in transcriptomics and RNA technologies have greatly expanded the repertoire of bacterial sRNAs and revealed their extensive roles in posttranscriptional regulatory networks. This review provides an updated framework for the biogenesis of bacterial sRNAs and their regulatory roles within posttranscriptional networks. Crucially, we describe the regulatory pathways controlling sRNA expression, including environmental signal sensing and regulation mediated by σ factors and transcription factors, to illustrate how sRNAs respond dynamically to changing conditions. Expanding beyond expression control, we further discuss the diverse roles of sRNA-mediated regulation in metabolic adaptation, stress responses, and bacterial virulence, emphasizing their importance in linking environmental changes to cellular phenotypes. Concurrently, we review current experimental and computational methods used for sRNA discovery and target identification. Overall, this review provides an integrated perspective on how bacterial sRNAs connect environmental sensing with adaptive cellular responses and highlights the broader significance of RNA-mediated regulation in bacterial physiology.
Zhengkai Yi, Xingning Xiao, Likou Zou et al.· FEMS Microbiology Reviews· 0 citations
The development of multicellular organisms relies on the precise establishment and stable inheritance of cell type-specific transcriptional programs without changes to the underlying DNA sequence. Polycomb group (PcG) proteins are evolutionarily conserved epigenetic repressors that govern developmental gene expression by assembling into multiprotein complexes to establish robust and spatiotemporally restricted transcriptional silencing. Since their discovery through the classic Polycomb mutant phenotype in Drosophila melanogaster, PcG proteins have become a central paradigm for understanding epigenetic regulation during animal development. Here, we synthesize current knowledge of the molecular composition and functional organization of the core Polycomb repressive complexes (PRC1 and PRC2) and the accessory complexes PhoRC, PR-DUB, and dRAF, with particular emphasis on canonical hierarchical recruitment and emerging noncanonical regulatory mechanisms of Polycomb-mediated gene repression. We further summarize the dynamic roles of PcG proteins across the Drosophila life cycle, from embryonic patterning and larval organogenesis to metamorphic transition and adult tissue homeostasis. By integrating recent advances from Drosophila studies, this review provides a comprehensive overview of the molecular mechanisms and developmental functions of PcG proteins while highlighting future directions for investigating the conserved epigenetic mechanisms governing metazoan development.
