Loss of high-mobility group N5 contributes to the promotion of human endometrial stromal cell decidualization.

PURPOSE: High-mobility group N (HMGN) proteins are the only non-histone proteins that specifically bind within the nucleosome between core histones and DNA. Among them, HMGN5 is one of the candidates that could participate in mouse endometrial decidualization; however, the specific role of HMGN5 remains to be clarified in human endometrial stromal cells (HESCs). METHODS: Primary HESCs were isolated from hysterectomy specimens and incubated with or without 8-bromo-cyclic adenosine monophosphate (8-br-cAMP) and medroxyprogesterone acetate (MPA). RESULTS: We demonstrated that HMGN5 expression in decidualized HESCs stimulated by 8-br-cAMP and MPA decreased significantly. The inhibition of HMGN5 expression by small interfering RNA (siRNA) induced the major decidual marker genes expression, including IGFBP1 (insulin-like growth factor binding protein 1) and PRL (prolactin). In addition, microRNA-542-3p (miR-542-3p), which was identified as a regulatory miRNA of IGFBP1 during decidualization, was significantly suppressed by HMGN5 siRNA. However, the expression of HMGN5 was not alternated by miR-542-3p overexpression. CONCLUSIONS: These findings suggest that the down-regulation of HMGN5 plays a role in the promotion of human endometrial stromal decidualization and acts upstream of miR-542-3p.