Histone deacetylase 6 negatively regulated microRNA-199a-5p induces the occurrence of preeclampsia by targeting VEGFA in vitro

Background: Preeclampsia (PE) is a special complication during pregnancy, which can cause severe maternal complications and lead the cause of maternal and perinatal death. So far, the etiology and pathogenesis of the disease is still not very clear. Currently, MicroRNAs (miRNAs) are reported to be the key regulators in the development of PE.

Methods: The miR-199a-5p expression was detected by qRT-PCR. The expression of vascular endothelial growth factor A (VEGFA), placental growth factor (PLGF) and activating transcription factor 3 (ATF-3) were detected by qRT-PCR and Western blot. Transwell-invasion assay wasused to assess the effects of miR-199a-5p, PLGF and ATF-3 on the invasion of HTR-8/SVneo and TEV-1cell lines. Western blot and qRT-PCR were used to assess the related molecular mechanisms. Dual luciferase reporter assay was used to detect the interaction between miR-199a-5p and VEGFA.

Results: Here, weinitially demonstrated that in PE tissues, miR-199a-5p expression was higher than that in normal tissues, while there was sharp reduction in VEGFA. In placental tissues of PE patients, miR-199a-5p exhibited a negatively correlation with VEGFA. The invasion of HTR-8/SVneo and TEV-1 cells was suppressed by miR-199a-5p through direct inhibition of VEGFA expression. In addition, PE tissues were associated with sharp reduction in the protein levels of PLGF, ATF-3 and histone deacetylase 6 (HDAC6) compared with the normal tissues. We further proved that over-expression of PLGF could also promote HTR-8/SVneo and TEV-1 cells invasion through up-regulating ATF-3 expression and down-regulating DNM3 opposite strand (DNM3os) and miR-199a-5p expression. Lastly, we also found that tubacin suppressed HTR-8/SVneo and TEV-1 cells invasion via regulation of miR-199a-5p and VEGFA expression.

Conclusion: Our data demonstrated the role of miR-199a-5p in the preeclampsia, and proved that miR-199a-5p could act as a potential therapeutic target for the treatment of PE.