ArticleMolecular therapy. Nucleic acids2021
CircSTK40 contributes to recurrent implantation failure via modulating the HSP90/AKT/FOXO1 axis.
Article in Molecular therapy. Nucleic acids, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- The molecular puzzle of recurrent implantation failure: integrating genetic, epigenetic, and immune mechanisms for precision reproductive medicine.Journal of assisted reproduction and genetics · 2026Review
- Circular RNA Vv-circCOR27 modulates thermotolerance through attenuating VvHSP90.2b-VvHsfA7a interaction in grapevine.The New phytologist · 2026Article
- Multidimensional regulatory architecture of endometrial receptivity and its translational implications for implantation failure.Frontiers in endocrinology · 2026Review
- Comprehensive transcriptomic profiling of dynamic endometrial alterations during different implantation stages in goats (Capra hircus).Journal of animal science · 2025Article
- hsa_circ_0004121 and hsa_circ_0030162 Differentially Expressed in Plasma of Patients with Recurrent Implantation Failure.Reports of biochemistry & molecular biology · 2024Article
- Basic Research Advances in China on Embryo Implantation, Placentation, and Parturition.Maternal-fetal medicine (Wolters Kluwer Health, Inc.) · 2024Article
- circSLC4A7 accelerates stemness and progression of gastric cancer by interacting with HSP90 to activate NOTCH1 signaling pathway.Cell death & disease · 2023Article
- Primary Cilia Restrain PI3K-AKT Signaling to Orchestrate Human Decidualization.International journal of molecular sciences · 2022Article
- CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR.Journal of hematology & oncology · 2022Article
- CircHGF suppressed cell proliferation and osteogenic differentiation of BMSCs in ONFH via inhibiting miR-25-3p binding to SMAD7.Molecular therapy. Nucleic acids · 2022Article
- Altered Expression of GABPB1-IT1 and SLC9A3-AS1 Long Non-Coding RNAs in Recurrent Implantation Failure.Journal of reproduction & infertilityArticle
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increasing evidence has revealed a close relationship between non-coding RNAs and recurrent implantation failure (RIF). However, the role of circular RNAs (circRNAs) in RIF pathogenesis remains largely unknown. Microarray analyses were used to identify the differentially expressed circRNA-circSTK40. Functional experiments, including decidualization induction and terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay, were performed to determine the effects of circSTK40 on human endometrial stromal cells (ESCs). The interactions between circSTK40 and proteins were investigated by RNA pull-down, RNA immunoprecipitation, and co-immunoprecipitation (coIP) assays. We observed that circSTK40 expression was upregulated in the RIF midluteal-phase endometrial samples. circSTK40 overexpression in ESCs inhibited the decidualization process but concurrently enhanced cell survival during stress. Mechanistically, circSTK40 directly bound to HSP90 and CLU, thus functioning as a scaffold to block their interactions and hinder the proteasomal degradation of HSP90. The resulting high levels of HSP90 led to the activation of the AKT pathway and downregulation of FOXO1 expression. Inhibitors of AKT (MK-2206) and HSP90 (17AAG) both abolished the effects of circSTK40 overexpression in ESCs and increased the decidualization levels in a dose-dependent manner. Our findings indicate a novel epigenetic mechanism for RIF pathogenesis involving circSTK40 activity and provide a foundation for targeted treatments in patients with low endometrial receptivity.
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