ArticleInternational journal of biological sciences2024
MANF Promotes Unexplained Recurrent Miscarriages by Interacting with NPM1 and Downregulating Trophoblast Cell Migration and Invasion.
Article in International journal of biological sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- METTL3-Mediated m6A Modification of ACTR2 Promotes Trophoblast Cell Growth, Migration and Invasion in Unexplained Recurrent Spontaneous Abortion.Cell biochemistry and biophysics · 2026Article
- The role of TLR2/MyD88/NF-κB pathway-mediated macrophage M1 polarization in recurrent spontaneous abortion associated with antiphospholipid syndrome.Human cell · 2026Article
- Daphnetin alleviates unexplained recurrent spontaneous abortion by regulating the NR4A1/BACH2 axis in mice.Biological research · 2025Article
- MIR193BHG inhibits the proliferation, migration and invasion of trophoblasts by upregulating p53.Experimental and therapeutic medicine · 2024Article
- Review
- Role of protein post-translational modifications in unexplained recurrent pregnancy loss.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciencesReview
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dysplasia and invasive defects in early trophoblasts contribute to unexplained recurrent miscarriages (URMs). Mesencephalic astrocyte-derived neurotrophic factor (MANF) inhibits migration and invasion in some cancer cells, but its role in pregnancy-related diseases remains unresolved. Here, we found that MANF levels in the peripheral blood and aborted tissue of URM women were higher than in normal controls, irrespective of pregnancy or miscarriage. We confirm the interaction between MANF and nucleophosmin 1 (NPM1) in trophoblasts of URM patients, which increases the ubiquitination degradation of NPM1, leading to upregulation of the p53 signaling pathway and inhibition of cell proliferation, migration, and invasion ability. Using a URM mouse model, we found that MANF downregulation resulted in reduced fetal resorption; however, concomitant NPM1 downregulation led to increased abortion rates. These data indicate that MANF triggers miscarriage via NPM1 downregulation and p53 activation. Thus, MANF downregulation or disruption of the MANF-NPM1 interaction could be targets for URM therapeutics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.