College of Veterinary Medicine, Northwest A&F University, Yangling, China.
Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, China.
FEBS J. 2019 May;286(9):1780-1795. doi: 10.1111/febs.14783. Epub 2019 Mar 12.
The long non-coding RNAs (lncRNAs) are known to transcriptionally regulate a wide spectrum of diseases. Here, we screened for potentially functional lncRNAs in a mammary epithelial cell model of bovine mastitis by RNA-Seq technology and identified a class of previously undetected mastitis-related lncRNAs. A novel lncRNA was widely expressed in a variety of bovine tissues with diverse relative abundance and had a relatively low expression in mammary tissue. Given its predicted target gene is TUBA1C, we name it lncRNA-TUB. We found a higher expression of lncRNA-TUB in mammary epithelial cells that received a proinflammatory stimulus compared to normal cells. Knockout of lncRNA-TUB by the CRISPR/Cas9 system revealed that it plays crucial roles in the morphological shape, proliferation, migration and β-casein secretion of mammary epithelial cells. In addition, lncRNA-TUB mediates Escherichia coli-induced inflammatory factor secretion and Staphylococcus aureus adhesion to epithelial cells. Our results suggest that the lncRNAs identified here function in bovine mastitis, and that lncRNA-TUB affects the basic biological characteristics and functions of bovine mammary epithelial cells in inflammatory conditions, providing valuable insights into the mechanisms of bovine mastitis.
长链非编码 RNA（lncRNA）被认为可以转录调控广泛的疾病。在这里，我们通过 RNA-Seq 技术在牛乳腺炎的乳腺上皮细胞模型中筛选出潜在的功能性 lncRNA，鉴定出一类以前未检测到的与乳腺炎相关的 lncRNA。一种新的 lncRNA 在多种牛组织中广泛表达，相对丰度不同，在乳腺组织中表达相对较低。鉴于其预测的靶基因是 TUBA1C，我们将其命名为 lncRNA-TUB。我们发现，与正常细胞相比，受到促炎刺激的乳腺上皮细胞中 lncRNA-TUB 的表达更高。CRISPR/Cas9 系统敲除 lncRNA-TUB 后发现，它在乳腺上皮细胞的形态、增殖、迁移和 β-酪蛋白分泌中起着至关重要的作用。此外，lncRNA-TUB 介导大肠杆菌诱导的炎症因子分泌和金黄色葡萄球菌与上皮细胞的黏附。我们的研究结果表明，这里鉴定的 lncRNA 参与了牛乳腺炎的发生，lncRNA-TUB 影响了牛乳腺上皮细胞在炎症条件下的基本生物学特征和功能，为牛乳腺炎的发病机制提供了有价值的见解。
