Aurora B x CDK1

Wuding chicken, an indigenous avian breed native to China, is known for its high-quality meat and eggs. However, it has a low egg production rate, poor reproductive traits, and strong broody behavior. Ovarian follicle development is essential for egg production and reproduction, being regulated by the hypothalamus-pituitary-ovary (HPO) axis. Despite its significance, the molecular mechanism of this process in Wuding chicken is still unclear. In this study, the expression profiles of the hypothalamus, pituitary and ovary of Wuding chickens during laying and brooding periods were sequenced and analyzed. A total of 590, 423 and 5371 differentially expressed genes were identified in these three tissues, respectively. We selected genes enriched in reproduction-related signaling pathways to construct a protein-protein interaction network. The network showed that there were 17 genes that were hub genes, including CDK1, CCNB1, CDK2, PLK1, CDC20, AURKB, MAD2L1, BUB1, CCNB3, FZR1, BUB1B, CDC6, CCNA1, MAPK11, MCM3, ESPL1 and CHEK1. After isolating and identifying follicular granulosa cells (GCs), we assessed the function of the hub Aurora Kinase B (AURKB) gene within the network. Overexpression and knockdown experiments confirmed that AURKB promoted the synthesis of steroid hormones, estradiol and progesterone, in GCs by regulating the expression of STAR, CYP19A1, HSD3B1, and PTGS2 genes. In addition, AURKB enhanced GC proliferation while inhibiting GC senescence and apoptosis. These findings indicate that AURKB plays a crucial role in follicular development in Wuding chickens, providing valuable insights into their reproductive biology and laying the foundation for improving their brooding characteristics.

Ataxia telangiectasia and Rad3-related (ATR) and checkpoint kinase 1 (Chk1) are crucial kinases in the DNA damage response (DDR) pathway. While the roles of ATR and Chk1 within the DDR are well established, their roles in mitosis are not fully understood. Here, we describe that the ATR-Chk1 pathway is rewired during mitosis to promote full CDK1 activity, starkly contrasting its role in interphase, where it inhibits CDK1 following DNA damage in human cells. In mitosis, Chk1 inhibits residual activity of PKMYT1 (Myt1) via direct phosphorylation at Serine 143. Partial loss of CDK1 activity caused by inhibition of mitotic Chk1 leads to different effects on mitotic progression than full CDK1 inhibition. It causes increased lagging chromosomes in part through loss of Aurora B activity. Thus, mitosis-specific ATR-Chk1 activity is necessary to promote faithful chromosome segregation by ensuring that CDK1 activity is maintained in mitosis.

Methyl eugenol (ME), a natural compound found in various essential oils, has recently been classified as a Group 2A carcinogen by the International Agency for Research on Cancer.

This study aims to investigate the potential molecular mechanisms and underlying ME‐induced hepatocellular carcinoma (HCC) in humans using network toxicology, molecular docking, and integrative bioinformatics approaches, including transcriptomic and survival analyses of human HCC datasets.

Enrichment analysis highlighted significant associations with pathways related to steroid metabolic processes, extracellular exosomes, and diverse binding activities. KEGG pathway enrichment further implicated metabolic pathways in ME‐induced HCC development. Integration of STRING and Cytoscape analyses identified 14 hub targets, including key proteins such as AURKB, CCNB1, CDK1, and PLK1. Molecular docking studies demonstrated weak binding affinities of ME to these targets compared to their specific inhibitors. However, microarray data and survival analyses of human HCC samples revealed that AURKB, CCNB1, CDK1, and PLK1 are upregulated in HCC, with higher expression levels correlating with poorer overall survival, particularly for CCNB1.

These findings suggest that ME exposure may enhance the expression of these genes in hepatocytes, disrupting the cell cycle and promoting proliferation. This study provides valuable insights into the molecular mechanisms of ME‐induced HCC in humans and highlights potential therapeutic targets, such as CCNB1, for further investigation.