tRF-1-31-Pro-AGG-1-M5 mediates STAT1 to regulate epithelial-mesenchymal transition in intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic disorder of pregnancy with no clear pathogenesis. As a novel non-coding RNA, the role of tRNA in ICP remains to be discovered. Plasma samples were collected from 8 cases of ICP (n = 4) and healthy pregnant women (n = 4) for high-throughput sequencing to screen for differentially expressed tRNAs. The tRF-1-31-Pro-AGG-1-M5 was an unknown tRF, was found to be significantly down-regulated in ICP tissues, plasma, and cells. STAT1, identified as a target gene of tRF-1-31-Pro-AGG-1-M5, exhibited significant downregulation in ICP placental tissue. The results of the dual luciferase assay showed a direct targeting relationship between tRF-1-31-Pro-AGG-1-M5 and STAT1. When the level of bile acid was increased, E-cadherin showed significant up-regulation, while N-cadherin and Vimentin showed significant down-regulation. In addition, the cell migration ability was significantly decreased. This study demonstrates that tRF-1-31-Pro-AGG-1-M5 mediated STAT1 inhibition of trophoblast epithelial mesenchymal transition (EMT) may be one of the pathogenic mechanisms of abnormal placental trophoblast function and adverse pregnancy outcomes in ICP.