miR-495通过HDAC2/p53/PUMA轴调控滋养层细胞功能参与子痫前期发病机制

Abstract

Linkage between microRNAs (miRNAs) and pre-eclampsia (PE) has been documented. Here, we focused on miR-495 in PE and its underlying mechanism in regulation of trophoblast cells. Expression of miR-495, HDAC2, p53 and PUMA was determined in collected placental tissue samples. Loss- and gain-function was performed to determine the roles of miR-495, HDAC2, p53, and PUMA in biological processes of HTR8/SVneo cells and primary trophoblast cells. The relationships among miR-495, HDAC2, and p53 were pinpointed. PE patients presented with higher expression of miR-495, p53, and PUMA in placental tissues, but lower HDAC2. miR-495 negatively targeted HDAC2 expression. HDAC2 suppressed p53 expression via deacetylation. Overexpression of miR-495, p53, or PUMA inhibited biological properties of HTR8/SVneo cells and primary trophoblast cells, while opposite trends were observed in response to oe-HDAC2. In conclusion, miR-495 knockdown can suppress p53/PUMA axis by targeting HDAC2 to enhance biological behaviors of trophoblast cells, which may prevent occurrence of PE.