LncRNA HULIB promotes LPS induced inflammatory response in bovine mammary epithelial cells via PP2AB

Bovine mastitis is regulated by genetic and environmental factors. Long non-coding RNAs (LncRNAs), which regulate various biological processes (immune system and biological development), have been found to play a role in bovine mammary inflammation responses. Here, a novel functional lncRNA, named lncRNA HULIB, was identified as a regulator during bovine mastitis. qRT-PCR and subcellular fractionation assays showed that lncRNA HULIB was significantly up-regulated in LPS-induced bMECs and was mainly localized in the cytoplasm. Gain- or loss-of-function experiments demonstrated that an increase in lncRNA HULIB expression elevated the expression of TLR4 and NF-κB1, which enhanced NF-κB activity, promoting the expression of pro-inflammatory cytokines (IL-6, IL-8, IL-1β, etc) and apoptosis-related genes (BAX, CASP9 and CASP3, etc), while the expression of proliferation-related genes (PCNA, Cyclin D1, Cyclin D2, CDK4 and CDK2) was down-regulated. Ultimately, these changes exacerbated the LPS-induced inflammatory response. Mechanistically, RNA pull-down and RNA immunoprecipitation (RIP) assays revealed that lncRNA HULIB could directly bind the PP2AB protein to regulate inflammatory responses. Overall, lncRNA HULIB is a pro-inflammatory regulator, and its silencing can alleviate the inflammatory responses of bMECs, providing a potential strategy for molecular therapy of bovine mastitis.