Disordered p53-MALAT1 pathway is associated with recurrent miscarriage.

Abstract

Recurrent miscarriage (RM) affects about 1% of couples; however, the etiologies of half of the cases remain unknown. P53, a negative cell cycle regulator, has been found to modulate the expression of several long noncoding RNAs (lncRNAs) and overexpressed p53 has been observed in RM patients. To investigate the relationship between p53 and lncRNAs in the pathogenesis of RM, we detected the expression of p53 and six candidate lncRNAs in the villous from 27 RM patients and paired healthy controls. We found the level of NEAT1 and MALAT1 was reduced significantly and only the MALAT1 level negatively correlated with p53 protein level. By luciferase assay, we confirmed that p53 repress MALAT1 expression through directly binding to the promoter region. Functional study by using human trophoblast cell HTR-8/SVneo, we observed that p53 overexpression lead to decreased cells proliferation, migration, invasion and increased apoptosis. Meanwhile, MALAT1 overexpression partially restored these function of p53 overexpression.