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.

MALAT1 recruited the E3 ubiquitin ligase FBXW7 to induce CRY2 ubiquitin‐mediated degradation and participated in trophoblast migration and invasion

“…Increasing evidence has shown that lncRNAs are involved in important biological processes, and the abnormal expression of lncRNAs has been implicated in the pathogenesis of RSA (Zhu et al, 2019). Research has shown that the level of MALAT1 is significantly reduced in villi from RM patients (Y. Wang et al, 2019). In this study, we also observed an obviously reduced expression of MALAT1 in the villous specimens from the RSA patients, which was consistent with that report.…”

Non-Coding RNAs Regulate Placental Trophoblast Function and Participate in Recurrent Abortion

“…studied the transcriptional regulation of lncRNA PVT1 and its effects on the biological behavior of trophoblasts, which might be related to the pathogenesis of RSA. A study (Wang et al, 2019)found that the levels of NEAT1 and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in tissue samples of patients with RSA were significantly decreased, and knockdown of the MALAT1 gene could lead to a decrease in proliferation and an increase in apoptosis of trophoblasts and primary chorionic trophoblasts.…”

Clinical and immunological aspects on recurrent pregnancy loss

“…Indeed, it has been shown that trophoblast dysfunction, due to compromised trophoblast infiltration and apoptosis, as well as multiple aberrant signal transduction pathways (64), could lead to adverse pregnancy outcomes, including uRPL (65). In detail, all the impaired pathways previously investigated in RPL trophoblast cells functions (including kisspeptin/GPR54 and PIBF/PR pathways, C4d and Bb, MBL, NOD1 and NOD2 via MAPK/p38 pathway, miR-27a-3p/USP25 axis, Fas and FasL, PKC protein, CCNA2, TWIST, Prototype and Chimera-Type Galectins, miR-520 and PARP1, BMAL1 via SP1-DNMT1/DAB2IP pathway, EIF5A1 via ARAF-mediated activation of integrin/ERK signaling pathway, Stathmin-1, peroxiredoxin2are) are linked to trophoblast migration, proliferation, invasion and apoptosis processes potentially relevant for RPL pathogenesis (64,(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76)(77)(78). Less is known about potential immunological impaired processes induced by trophoblast dysfunction.…”