AURKB promotes colorectal cancer progression by triggering the phosphorylation of histone H3 at serine 10 to activate CCNE1 expression.

Aurora kinase B (AURKB) initiates the phosphorylation of serine 10 on histone H3 (pH3S10), a crucial process for chromosome condensation and cytokinesis in mammalian mitosis. Nonetheless, the precise mechanisms through which AURKB regulates the cell cycle and contributes to tumorigenesis as an oncogenic factor in colorectal cancer (CRC) remain unclear. Here, we report that AURKB was highly expressed and positively correlated with Ki-67 expression in CRC. The abundant expression of AURKB promotes the growth of CRC cells and xenograft tumors in animal model. AURKB knockdown substantially suppressed CRC proliferation and triggered cell cycle arrest in G2/M phase. Interestingly, cyclin E1 (CCNE1) was discovered as a direct downstream target of AURKB and functioned synergistically with AURKB to promote CRC cell proliferation. Mechanically, AURKB activated CCNE1 expression by triggering pH3S10 in the promoter region of CCNE1. Furthermore, it was showed that the inhibitor specific for AURKB (AZD1152) can suppress CCNE1 expression in CRC cells and inhibit tumor cell growth. To conclude, this research demonstrates that AURKB accelerated the tumorigenesis of CRC through its potential to epigenetically activate CCNE1 expression, suggesting AURKB as a promising therapeutic target in CRC.

Effect of the supplementation of exogenous complex non-starch polysaccharidases on the growth performance, rumen fermentation and microflora of fattening sheep.

The objective of this study was to evaluate the effects of exogenous non-starch polysaccharidases (a mixture of cellulase, xylanase, ß-glucanase and mannanase) on the growth performance and nutrient digestibility, rumen fermentation, and rumen microflora of sheep. The animal trial was conducted using 36 5-month-old female fattening hybrid sheep (Duolang♂ × Hu♀) who were randomly assigned into four groups comprising nine sheep per treatment: CON, T1, T2, and T3, with 0, 0.1, 0.3, and 0.5% NSPases/kg DM of TMR, respectively. This complex enzyme product was screened for optimal ratios based on previous in vitro tests and responded positively to the in vitro fermentation of the TMR. When treated with NSPases, there was a non-linear effect of average daily gain and feed conversion rate, with the greatest improvement observed in the T2 group. There were no significant differences (p > 0.05) in nutrient intake or apparent digestibility among the NSPase-supplemented groups. In addition, T2 group had a significantly higher acetate to propionate ratio and pH (p < 0.05) than the other groups, and NH3-N and microbial protein concentrations showed a quadratic curve. The results revealed that both immunoglobulins and serum hormones increased linearly with addition (p < 0.05). As the T2 group showed the best growth performance, the CON and T2 groups were subjected to rumen metagenomic analysis. The results showed higher abundance of bacteria and lower abundance of Viruses in the rumen microbiota of the T2 group compared to the CON group. In addition, Uroviricota and Proteobacteria abundance was significantly lower in the T2 group than in the CON group at the phylum level (p < 0.05). These results suggest that the supplementation of high-concentrate rations with NSPases enhance immunity, reduces virus abundance in the rumen, improves rumen health, and promotes rumen fermentation. Our findings provide novel insights for improving growth performance and alleviating inflammatory responses arising from high concentrate feeding patterns in ruminants. However, the biological mechanisms cannot be elucidated by exploring the composition of rumen microbe alone, and further studies are required.

Tumor neoantigens derived from RNA editing events show significant clinical relevance in melanoma patients treated with immunotherapy.

This study aimed to investigate the clinical significance of RNA editing (RE) and RNA editing derived (RED-) neoantigens in melanoma patients treated with immunotherapy. Vardict and VEP were used to identify the somatic mutations. RE events were identified by Reditools2 and filtered by the custom pipeline. miRTar2GO was implemented to predict the RE whether located in miRNA targets within the 3' UTR region. NetMHCpan and NetCTLpan were used to identify and characterize RED-neoantigens. In total, 7116 RE events were identified, most of which were A-to-I events. Using our custom pipeline, 631 RED-neoantigens were identified that show a significantly greater peptide-MHC affinity, and facilitate epitope processing and presentation than wild-type peptides. The OS of the patients with high RED-neoantigens burden was significantly longer ( P  = 0.035), and a significantly higher RED-neoantigens burden was observed in responders ( P  = 0.048). The area under the curve of the RED-neoantigen was 0.831 of OS. Then, we validated the reliability of RED-neoantigens in predicting the prognosis in an independent cohort and found that patients with high RED-neoantigens exhibited a longer OS ( P  = 0.008). To our knowledge, this is the first study to systematically assess the clinical relevance of RED-neoantigens in melanoma patients treated with immunotherapy.