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  • Springer Science and Business Media LLC  (4)
  • Chen, Lu  (4)
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  • Springer Science and Business Media LLC  (4)
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  • 1
    Online Resource
    Online Resource
    Exosomal YB-1 facilitates ovarian restoration by MALAT1/miR-211-5p/FOXO3 axis
    Springer Science and Business Media LLC ; 2024
    In:  Cell Biology and Toxicology Vol. 40, No. 1 ( 2024-05-03)
    Details
    In: Cell Biology and Toxicology, Springer Science and Business Media LLC, Vol. 40, No. 1 ( 2024-05-03)
    Abstract: Premature ovarian failure (POF) affects many adult women less than 40 years of age and leads to infertility. Mesenchymal stem cells-derived small extracellular vesicles (MSCs-sEVs) are attractive candidates for ovarian function restoration and folliculogenesis for POF due to their safety and efficacy, however, the key mediator in MSCs-sEVs that modulates this response and underlying mechanisms remains elusive. Herein, we reported that YB-1 protein was markedly downregulated in vitro and in vivo models of POF induced with H 2 O 2 and CTX respectively, accompanied by granulosa cells (GCs) senescence phenotype. Notably, BMSCs-sEVs transplantation upregulated YB-1, attenuated oxidative damage-induced cellular senescence in GCs, and significantly improved the ovarian function of POF rats, but that was reversed by YB-1 depletion. Moreover, YB-1 showed an obvious decline in serum and GCs in POF patients. Mechanistically, YB-1 as an RNA-binding protein (RBP) physically interacted with a long non-coding RNA, MALAT1, and increased its stability, further, MALAT1 acted as a competing endogenous RNA (ceRNA) to elevate FOXO 3 levels by sequestering miR-211-5p to prevent its degradation, leading to repair of ovarian function. In summary, we demonstrated that BMSCs-sEVs improve ovarian function by releasing YB-1, which mediates MALAT1/miR-211-5p/FOXO 3 axis regulation, providing a possible therapeutic target for patients with POF.
    Type of Medium: Online Resource
    ISSN: 1573-6822
    URL: Article
    DOI: 10.1007/s10565-024-09871-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 1496562-8
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  • 2
    Online Resource
    Online Resource
    A methylation- and immune-related lncRNA signature to predict ovarian cancer outcome and uncover mechanisms of chemoresistance
    Springer Science and Business Media LLC ; 2023
    In:  Journal of Ovarian Research Vol. 16, No. 1 ( 2023-09-06)
    Details
    In: Journal of Ovarian Research, Springer Science and Business Media LLC, Vol. 16, No. 1 ( 2023-09-06)
    Abstract: Tumor-associated lncRNAs regulated by epigenetic modification switches mediate immune escape and chemoresistance in ovarian cancer (OC). However, the underlying mechanisms and concrete targets have not been systematically elucidated. Here, we discovered that methylation modifications played a significant role in regulating immune cell infiltration and sensitizing OC to chemotherapy by modulating immune-related lncRNAs (irlncRNAs), which represent tumor immune status. Through deep analysis of the TCGA database, a prognostic risk model incorporating four methylation-related lncRNAs (mrlncRNAs) and irlncRNAs was constructed. Twenty-one mrlncRNA/irlncRNA pairs were identified that were significantly related to the overall survival (OS) of OC patients. Subsequently, we selected four lncRNAs to construct a risk signature predictive of OS and indicative of OC immune infiltration, and verified the robustness of the risk signature in an internal validation set. The risk score was an independent prognostic factor for OC prognosis, which was demonstrated via multifactorial Cox regression analysis and nomogram. Moreover, risk scores were negatively related to the expression of CD274, CTLA4, ICOS, LAG3, PDCD1, and PDCD1LG2 and negatively correlated with CD8 + , CD4 + , and Treg tumor-infiltrating immune cells. In addition, a high-risk score was associated with a higher IC50 value for cisplatin, which was associated with a significantly worse clinical outcome. Next, a competing endogenous RNA (ceRNA) network and a signaling pathway controlling the infiltration of CD8 + T cells were explored based on the lncRNA model, which suggested a potential therapeutic target for immunotherapy. Overall, this study constructed a prognostic model by pairing mrlncRNAs and irlncRNAs and revealed the critical role of the FTO/RP5-991G20.1/hsa-miR-1976/MEIS1 signaling pathway in regulating immune function and enhancing anticancer therapy.
    Type of Medium: Online Resource
    ISSN: 1757-2215
    URL: Article
    DOI: 10.1186/s13048-023-01260-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2455679-8
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  • 3
    Online Resource
    Online Resource
    SIAH1 reverses chemoresistance in epithelial ovarian cancer via ubiquitination of YBX-1
    Springer Science and Business Media LLC ; 2022
    In:  Oncogenesis Vol. 11, No. 1 ( 2022-03-10)
    Details
    In: Oncogenesis, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2022-03-10)
    Abstract: Chemoresistance is a severe outcome among patients with epithelial ovarian cancer (EOC) that leads to a poor prognosis. YBX-1 has been shown to cause treatment failure and cancer progression in EOC. However, strategies that directly target YBX-1 are not yet conceivable. Here, we identified that SIAH1 which was downregulated in chemoresistant EOC samples and cell lines functioned as novel E3 ligases to trigger degradation of YBX-1 at cytoplasm by RING finger domain. Mechanistic studies show that YBX-1 was ubiquitinated by SIAH1 at lys304 that lead to the instability of its target m5C-modified mRNAs, thus sensitized EOC cells to cDDP. Overexpression of SIAH1 enhanced the antitumor efficacy of cisplatin in vitro and in vivo, which were partially impaired by ectopic expression of YBX-1 or depletion of YBX-1 ubiquitination. In summary, our data identify the SIAH1/YBX-1 interaction as a therapeutic target for overcoming EOC chemoresistance.
    Type of Medium: Online Resource
    ISSN: 2157-9024
    URL: Article
    DOI: 10.1038/s41389-022-00387-6
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2674437-5
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  • 4
    Online Resource
    Online Resource
    EIF4A3-Induced Exosomal circLRRC8A Alleviates Granulosa Cells Senescence Via the miR-125a-3p/NFE2L1 axis
    Springer Science and Business Media LLC ; 2023
    In:  Stem Cell Reviews and Reports Vol. 19, No. 6 ( 2023-08), p. 1994-2012
    Details
    In: Stem Cell Reviews and Reports, Springer Science and Business Media LLC, Vol. 19, No. 6 ( 2023-08), p. 1994-2012
    Abstract: Premature ovarian failure (POF) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Mesenchymal stromal cells-derived exosomes (MSCs-Exos) have an essential role in the treatment of reproductive disorders, particularly POF. However, the biological function and therapeutic mechanism of MSCs exosomal circRNAs in POF remain to be determined. Here, with bioinformatics analysis and functional assays, circLRRC8A was found to be downregulated in senescent granulosa cells (GCs) and acted as a crucial factor in MSCs-Exos for oxidative damage protection and anti-senescence of GCs in vitro and in vivo. Mechanistic investigations revealed that circLRRC8A served as an endogenous miR-125a-3p sponge to downregulate NFE2L1 expression. Moreover, eukaryotic initiation factor 4A3 (EIF4A3), acting as a pre-mRNA splicing factor, promoted circLRRC8A cyclization and expression by directly binding to the LRRC8A mRNA transcript. Notably, EIF4A3 silencing reduced circLRRC8A expression and attenuated the therapeutic effect of MSCs-Exos on oxidatively damaged GCs. This study demonstrates a new therapeutic pathway for cellular senescence protection against oxidative damage by delivering circLRRC8A-enriched exosomes through the circLRRC8A/miR-125a-3p/NFE2L1 axis and paves the way for the establishment of a cell-free therapeutic approach for POF. CircLRRC8A may be a promising circulating biomarker for diagnosis and prognosis and an exceptional candidate for further therapeutic exploration. Graphical Abstract
    Type of Medium: Online Resource
    ISSN: 2629-3269 , 2629-3277
    URL: Article
    DOI: 10.1007/s12015-023-10564-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2495579-6
    SSG: 12
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