Metformin has been reported to be involved in the pathogenesis of PE (pre-eclampsia). This study aims to investigate the molecular mechanism of how UCA1 interferes with MMP9 expression under the influence of metformin, which contributes to the development of pre-eclampsia. Transwell assay was utilized to examine effect of Met (Metformin) on cell migration, and real-time PCR, western-blot analysis and IHC (Immunohistochemistry) were carried out to determine effect of Met on expressions of UCA1, miR-204 and MMP9, as well as compare UCA1, miR-204 and MMP9 level in different groups. Computational analysis and luciferase assay were performed to detect interaction among UCA1, miR-204 and MMP9. Met evidently inhibited the migration of HUVEC and HPASMC cells, and UCA1 and MMP9 levels showed a stepwise decline, while miR-204 level displayed a gradual increase as the concentration of Met increased when compared with the negative controls. Result of computational analysis showed that miR-204 directly bound to UCAl. Meanwhile, MMP9 was identified as a virtual target gene of miR-204. Result of protein were observed in pre-eclampsia (+) group compared with pre-eclampsia (-) group, while miR-204 level in pre-eclampsia (+) group was significantly lower than pre-eclampsia (-) group. Taken together, we found that administration of metformin prevents pre-eclampsia by suppressing migration of trophoblast cells via modulating the signaling pathway of UCA1/miR-204/MMP-9. (C) 2019 Published by Elsevier Inc.