The TGF-β/UCHL5/Smad2 Axis Contributes to the Pathogenesis of Placenta Accreta

Hashimoto, Kei; Miyagawa, Yuko; Watanabe, Saya; Takasaki, Kazuki; Nishizawa, Miki; Yatsuki, Keita; Takahashi, Yuko; Kamata, Hideo; Kihira, Chikara; Hiraike, Haruko; Sasamori, Yukifumi; Kido, Koichiro; Ryo, Eiji; Nagasaka, Kazunori

doi:10.3390/ijms241813706

Cited by 2 publications

(2 citation statements)

References 46 publications

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“…[ 61 ] The clinical development of DUB inhibitors is challenging, and most DUB inhibitors are in preclinical development. [ 61 , 62 , 63 , 64 ] Two DUB small molecule inhibitors (VLX1570 and KSQ‐4279) have entered phase I clinical trials in malignant tumors (NCT02372240 and NCT05240898). However, these clinical trials have not yet achieved sufficiently good results.…”

Section: Discussionmentioning

confidence: 99%

EZH2 Inhibition Enhances PD‐L1 Protein Stability Through USP22‐Mediated Deubiquitination in Colorectal Cancer

Huang,

Yin,

Wang

et al. 2024

Advanced Science

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The regulation of PD‐L1 is the key question, which largely determines the outcome of the immune checkpoint inhibitors (ICIs) based therapy. However, besides the transcription level, the protein stability of PD‐L1 is closely correlated with its function and has drawn increasing attention. In this study, EZH2 inhibition enhances PD‐L1 expression and protein stability, and the deubiquitinase ubiquitin‐specific peptidase 22 (USP22) is identified as a key mediator in this process. EZH2 inhibition transcriptionally upregulates USP22 expression, and upregulated USP22 further stabilizes PD‐L1. Importantly, a combination of EZH2 inhibitors with anti‐PD‐1 immune checkpoint blockade therapy improves the tumor microenvironment, enhances sensitivity to immunotherapy, and exerts synergistic anticancer effects. In addition, knocking down USP22 can potentially enhance the therapeutic efficacy of EZH2 inhibitors on colon cancer. These findings unveil the novel role of EZH2 inhibitors in tumor immune evasion by upregulating PD‐L1, and this drawback can be compensated by combining ICI immunotherapy. Therefore, these findings provide valuable insights into the EZH2‐USP22‐PD‐L1 regulatory axis, shedding light on the optimization of combining both immune checkpoint blockade and EZH2 inhibitor‐based epigenetic therapies to achieve more efficacies and accuracy in cancer treatment.

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Section: Discussionmentioning

confidence: 99%

EZH2 Inhibition Enhances PD‐L1 Protein Stability Through USP22‐Mediated Deubiquitination in Colorectal Cancer

Huang,

Yin,

Wang

et al. 2024

Advanced Science

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“…However, whether impaired mitochondrial function also occurs in placenta accreta remain incompletely understood. In recent years, candidate molecules that may influence the development and progression of placenta accreta are beginning to be identified [20]. We hypothesize that these molecular markers may be directly or indirectly related to mitochondrial function.…”

Section: Introductionmentioning

confidence: 99%

Current understanding of the pathogenesis of placenta accreta spectrum disorder with focus on mitochondrial function

Kobayashi,

Matsubara,

Yoshimoto

et al. 2024

J of Obstet and Gynaecol

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AimThe refinement of assisted reproductive technology, including the development of cryopreservation techniques (vitrification) and ovarian stimulation protocols, makes frozen embryo transfer (FET) an alternative to fresh ET and has contributed to the success of assisted reproductive technology. Compared with fresh ET cycles, FET cycles were associated with better in vitro fertilization outcomes; however, the occurrence of pregnancy‐induced hypertension, preeclampsia, and placenta accreta spectrum (PAS) was higher in FET cycles. PAS has been increasing steadily in incidence as a life‐threatening condition along with cesarean rates worldwide. In this review, we summarize the current understanding of the pathogenesis of PAS and discuss future research directions.MethodsA literature search was performed in the PubMed and Google Scholar databases.ResultsRisk factors associated with PAS incidence include a primary defect of the decidua basalis or scar dehiscence, aberrant vascular remodeling, and abnormally invasive trophoblasts, or a combination thereof. Freezing, thawing, and hormone replacement manipulations have been shown to affect multiple cellular pathways, including cell proliferation, invasion, epithelial‐to‐mesenchymal transition (EMT), and mitochondrial function. Molecules involved in abnormal migration and EMT of extravillous trophoblast cells are beginning to be identified in PAS placentas. Many of these molecules were also found to be involved in mitochondrial biogenesis and dynamics.ConclusionThe etiology of PAS may be a multifactorial genesis with intrinsic predisposition (e.g., placental abnormalities) and certain environmental factors (e.g., defective decidua) as triggers for its development. A distinctive feature of this review is its focus on the potential factors linking mitochondrial function to PAS development.

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The TGF-β/UCHL5/Smad2 Axis Contributes to the Pathogenesis of Placenta Accreta

Cited by 2 publications

References 46 publications

EZH2 Inhibition Enhances PD‐L1 Protein Stability Through USP22‐Mediated Deubiquitination in Colorectal Cancer

EZH2 Inhibition Enhances PD‐L1 Protein Stability Through USP22‐Mediated Deubiquitination in Colorectal Cancer

Current understanding of the pathogenesis of placenta accreta spectrum disorder with focus on mitochondrial function

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