A mutator-derived prognostic eRNA signature provides insight into the pathogenesis of breast cancer.

Abundant evidence suggests that enhancer RNA (eRNA) is closely related to tumorigenesis, and the role of eRNA transcription in promoting genomic instability in cancers is gradually unveiled. However, research on the evaluation of the prognostic value and molecular mechanisms of genomic instability associated eRNAs in breast cancer is long overdue. Here, we integratively analyzed eRNA expression and somatic mutation profiles in breast cancer genome. We identified genomic instability associated eRNAs and developed a prognostic signature based on these eRNAs with the area under the curve (AUC) around 0.8 at 9-year survival. We further found the prognostic value of this signature is independent of common clinical factors and is better than TP53 status. Higher expression of genomic instability associated genes in the high-risk group was observed, suggesting that this eRNA signature may serve as an indicator of genomic instability in breast cancer. We found prognostic eRNA co-expressed genes are mainly enriched in Gene set 'Breast Cancer 8P12-P11 Amplicon', Gene set 'Metabolism of lipids' and GO process 'Ubiquitin protein ligase binding'. Furthermore, 11 eRNA-signature regulated genes are identified by assessing promoter-enhancer interaction. Among these genes, F11R, BHLHE40, and NECTIN4 are previously reported oncogenes and EGOT is a tumor suppressor gene, indicating the direct roles of eRNAs in tumorigenesis.

Comparative evaluation of the fecal microbiota of adult hybrid pigs and Tibetan pigs, and dynamic changes in the fecal microbiota of hybrid pigs.

The breed of pig can affect the diversity and composition of fecal microbiota, but there is a lack of research on the fecal microbiota of hybrid pigs. In this study, feces samples from Chuanxiang black pigs (a hybrid of Tibetan and Duroc pigs) aged 3 days (n = 24), 70 days (n = 31), 10 months (n = 13) and 2 years (n = 30) and Tibetan pigs aged 10 months (n = 14) and 2 years (n = 15) were collected and sequenced by 16S rRNA gene sequencing technology. We also measured the weight of all the tested pigs and found that the 10-month-old and two-year-old Chuanxiang black pigs weighed about three times the weight of Tibetan pigs of the same age. After comparing the genus-level microbiota composition of Tibetan pigs and Chuanxiang black pigs at 10 months and two years of age, we found that Treponema and Streptococcus were the two most abundant bacteria in Chuanxiang black pigs, while Treponema and Chirstensenellaceae_R.7_group were the two most abundant bacteria in Tibetan pigs. Prediction of microbial community function in adult Chuanxiang black pigs and Tibetan pigs showed changes in nutrient absorption, disease resistance, and coarse feeding tolerance. In addition, we also studied the changes in fecal microbiota in Chuanxiang black pigs at 3 days, 70 days, 10 months, and 2 years of age. We found that the ecologically dominant bacteria in fecal microbiota of Chuanxiang black pigs changed across developmental stages. For example, the highest relative abundance of 70-day-old Chuanxiang black pigs at the genus level was Prevotella. We identified specific microbiota with high abundance at different ages for Chuanxiang black pigs, and revealed that the potential functions of these specific microbiota were related to the dominant phenotype such as fast growth rate and strong disease resistance. Our findings help to expand the understanding of the fecal microbiota of hybrid pigs and provide a reference for future breeding and management of hybrid pigs.