Long non-coding RNA HOX transcript antisense RNA (HOTAIR) suppresses the angiogenesis of human placentation by inhibiting vascular endothelial growth factor A expression.

Abstract

HOX transcript antisense RNA (HOTAIR) is a long non-coding RNA located within the Homeobox C (HOXC) gene cluster on chromosome 12. Previous studies have revealed that HOTAIR is overexpressed in many types of cancers and is associated with metastasis and poor survival rates; however, few reports have mentioned the relationship between HOTAIR and angiogenesis of the human placenta. The aim of the present study was to investigate the correlation between HOTAIR and vascular endothelial growth factor (VEGF) A in the human placenta. HOTAIR levels decreased significantly in human placenta with increasing gestational age, and were negatively correlated with VEGFA levels. Invitro assays revealed that HOTAIR overexpression suppressed the proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs); however, inhibition of HOTAIR had the opposite effects. Furthermore, VEGFA overexpression reversed the inhibitory effect of HOTAIR on the proliferation, migration, invasion and tube formation of HUVECs. In addition, overexpression of HOTAIR significantly inhibited VEGFA expression. Notably, a luciferase reporter assay found that HOTAIR inhibited VEGFA transcription by directly targeting the VEGFA promoter. Together, these results suggest that HOTAIR plays an important role in suppressing angiogenesis of the human placenta by inhibiting the expression of VEGFA; thus, HOTAIR may represent a potential therapeutic target for patients with human placental vascularisation abnormalities.