Effect of the p53–tristetraprolin–stathmin-1 pathway on trophoblasts at maternal–fetal interface

Abstract

ProblemTo reveal the effect of p53–tristetraprolin–stathmin-1 signaling on trophoblasts and recurrent spontaneous abortion (RSA).Method of studyStathmin-1 (STMN1), p53, and tristetraprolin (TTP) expression in paraffin-embedded villus tissue was determined using immunohistochemistry. HTR-8/SVneo cells were treated with doxorubicin to activate p53; STMN1 and TTP levels were detected by quantitative reverse transcription–PCR and western blotting. Western blotting and immunofluorescence were used to investigate STMN1 expression after TTP overexpression or knockdown in HTR-8 cells.ResultsSTMN1 was downregulated and p53 was upregulated in the villus tissue from patients with RSA. Doxorubicin decreased STMN1 expression but enhanced TTP expression in HTR-8 cells. In vitro, TTP overexpression inhibited STMN1 production; TTP knockdown promoted it. TTP downregulated STMN1 expression in trophoblasts by directly binding its 3ʹ untranslated region.ConclusionsTTP modulates trophoblast function and interacts with STMN1 and p53, and is related to pregnancy outcomes.

RETRACTED: Elevated Tristetraprolin Impairs Trophoblast Invasion in Women with Recurrent Miscarriage by Destabilization of HOTAIR

“… 24 Recently, we reported TTP expression is increased in trophoblasts from patients with RM compared to healthy controls. 25 Moreover, Kasra Khalaj et al. 26 showed that TTP protein was downregulated in an LPS-induced mouse pregnancy loss model, and its targets TNF-α and interleukin-6 (IL-6) were upregulated.…”

PRDM4 inhibits cell proliferation and tumorigenesis by inactivating the PI3K/AKT signaling pathway through targeting of PTEN in cervical carcinoma

“…Cyclin D1, as a cell proliferation promoter, has been confirmed in different types of cancers [ 26 ]. Additionally, the strong and widespread roles of p53 and p21 in regulating cell invasion and proliferation in several types of cancers and trophoblasts have been confirmed, and cervical cancer cells modified by PRDM4 show similar biological behavior [ 27 ].…”

Chorionic villus‐derived mesenchymal stem cells induce E3 ligase TRIM72 expression and regulate cell behaviors through ubiquitination of p53 in trophoblasts

“…Placental apoptosis is aggravated in placentas obtained from pregnancies with preeclampsia; this finding is associated with upregulation of p53, a well-studied tumor suppressor. Several studies have confirmed that suppression of P53 signal reduces both early and late trophoblast apoptosis, 25,26 and subsequently alleviate preeclampsia induced by trophoblast. In this study, we confirmed for the first time that TRIM72, which is overexpressed after treatment of CVMSCs-derived exosomes, can bind to P53 and promote P53 degradation in consistency with the previous report, and after P53 expression is reduced, the apoptosis rate of trophoblast is also decreased.…”