Ubiquitin C‐terminal hydrolase L1 (UCHL1), a double‐edged sword in mammalian oocyte maturation and spermatogenesis

Yang, Donghui; Lu, Qizhong; Peng, Sha; Hua, Jinlian

doi:10.1111/cpr.13347

Cited by 11 publications

(6 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At the same time, it promotes tumor metastasis in cancers like nasopharyngeal cancer, breast cancer, lung cancer, and others ( Rolland et al, 2014 ; Cerqueira et al, 2015 ; Meng et al, 2017 ). UCHL1, Ubiquitin C-Terminal Hydrolase L1, which has been extensively studied in tumors such as lung and breast cancer as well as colorectal cancer ( Yang et al, 2022 ), plays a catalytic role in colorectal cancer ( Zhong et al, 2012 ). PODXL, whose overexpression promotes pancreatic cancer development ( Taniuchi et al, 2022 ); TGF and its mediated PODXL, like the previously mentioned genes, play corresponding roles in colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

Subtypes analysis and prognostic model construction based on lysosome-related genes in colon adenocarcinoma

Yang

Huang

et al. 2023

Front. Genet.

View full text Add to dashboard Cite

Background: Lysosomes are essential for the development and recurrence of cancer. The relationship between a single lysosome-related gene and cancer has previously been studied, but the relationship between the lysosome-related genes (LRGs) and colon adenocarcinoma (COAD) remains unknown. This research examined the role of lysosome-related genes in colon adenocarcinoma.Methods: 28 lysosome-related genes associated with prognosis (PLRGs) were found by fusing the gene set that is differently expressed between tumor and non-tumor in colon adenocarcinoma with the gene set that is related to lysosomes. Using consensus unsupervised clustering of PLRGs, the colon adenocarcinoma cohort was divided into two subtypes. Prognostic and tumor microenvironment (TME) comparisons between the two subtypes were then made. The PLRGs_score was constructed using the least absolute shrinkage and selection operator regression (LASSO) method to quantify each patient’s prognosis and provide advice for treatment. Lastly, Western Blot and immunohistochemistry (IHC) were used to identify MOGS expression at the protein level in colon adenocarcinoma tissues.Results: PLRGs had more somatic mutations and changes in genetic level, and the outcomes of the two subtypes differed significantly in terms of prognosis, tumor microenvironment, and enrichment pathways. Then, PLRGs_score was established based on two clusters of differential genes in the cancer genome atlas (TCGA) database, and external verification was performed using the gene expression omnibus (GEO) database. Then, we developed a highly accurate nomogram to enhance the clinical applicability of the PLRGs_score. Finally, a higher PLRGs_score was associated with a poorer overall survival (OS), a lower tumor mutation burden (TMB), a lower cancer stem cell (CSC) index, more microsatellite stability (MSS), and a higher clinical stage. MOGS was substantially elevated at the protein level in colon adenocarcinoma as additional confirmation.Conclusion: Overall, based on PLRGs, we identified two subtypes that varied significantly in terms of prognosis and tumor microenvironment. Then, in order to forecast patient prognosis and make treatment suggestions, we developed a diagnostic model with major significance for prognosis, clinical relevance, and immunotherapy. Moreover, we were the first to demonstrate that MOGS is highly expressed in colon adenocarcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Subtypes analysis and prognostic model construction based on lysosome-related genes in colon adenocarcinoma

Yang

Huang

et al. 2023

Front. Genet.

View full text Add to dashboard Cite

show abstract

“…The numbers of spermatogenic cells (Figure 4A,B) and proliferative marker PCNA‐ and Ki67‐positive cells (Figure 4G,H) significantly decreased, and that of TUNEL‐positive cells increased (Figure 4D), accompanied by an inflammatory response (Figure S3D,E), indicating that the function of UCHL1 is to maintain the homeostatic balance of SSCs in vitro and in vivo. However, UCHL1 is a double‐edged sword, and an imbalance in its expression level will affect the normal physiological and biological processes of cells and organisms 47 . Studies have shown that overexpression of UCHL1 in transgenic mice could lead to sterility and severely affect the formation of spermatocytes, thus affecting the spermatogenesis process 48 .…”

Section: Discussionmentioning

confidence: 99%

“…However, UCHL1 is a double-edged sword, and an imbalance in its expression level will affect the normal physiological and biological processes of cells and organisms. 47 Studies have shown that overexpression of UCHL1 in transgenic mice could lead to sterility and severely affect the formation of spermatocytes, thus affecting the spermatogenesis process. 48 However, UCHL1 box deletion mutant gad mice exhibit seminiferous tubule atrophy, lumen cell apoptosis, other cell enlargement, and PCNA-positive cell decreases.…”

Section: Discussionmentioning

confidence: 99%

UCHL1 maintains microenvironmental homeostasis in goat germline stem cells

Yang,

Zhang,

Chen

et al. 2023

The FASEB Journal

Self Cite

View full text Add to dashboard Cite

Spermatogonial stem cells (SSCs) play a crucial role in mammalian spermatogenesis and maintain the stable inheritance of the germline in livestock. However, stress and bacterial or viral infections can disrupt immune homeostasis of the testes, thereby leading to spermatogenesis destruction and infertility, which severely affects the health and productivity of mammals. This study aimed to explore the effect of ubiquitin C‐terminal hydrolase L1 (UCHL1) knockdown (KD) in goat SSCs and mouse testes and investigate the potential anti‐inflammatory function of UCHL1 in a poly(I:C)‐induced inflammation model to maintain microenvironmental homeostasis. In vitro, the downregulation of UCHL1 (UCHL1 KD) in goat SSCs increased the expression levels of apoptosis and inflammatory factors and inhibited the self‐renewal and proliferation of SSCs. In vivo, the structure of seminiferous tubules and spermatogenic cells was disrupted after UCHL1 KD, and the expression levels of apoptosis‐ and inflammation‐related proteins were significantly upregulated. Furthermore, UCHL1 inhibited the TLR3/TBK1/IRF3 pathway to resist poly(I:C)‐induced inflammation in SSCs by antagonizing HSPA8 and thus maintaining SSC autoimmune homeostasis. Most importantly, the results of this study showed that UCHL1 maintained immune homeostasis of SSCs and spermatogenesis. UCHL1 KD not only inhibited the self‐renewal and proliferation of goat SSCs and spermatogenesis but was also involved in the inflammatory response of goat SSCs. Additionally, UCHL1 has an antiviral function in SSCs by antagonizing HSPA8, which provides an important basis for exploring the specific mechanisms of UCHL1 in goat spermatogenesis.

show abstract

“…Our previous study revealed that UCHL1 negatively regulated the immunosuppressive activity of mesenchymal stem cells [ 22 ]. Additionally, within the mammalian reproductive system, UCHL1 plays an essential regulatory role in controlling mammalian oocyte development and spermatogenesis [ 23 ]. A recent finding reveals that within the uterus during early pregnancy of mice, UCHL1 is specifically expressed in decidual cells [ 24 ]; however, the roles of UCHL1 have not been explored in miscarriage related to impaired decidualization.…”

Section: Introductionmentioning

confidence: 99%

Deficiency of UCHL1 results in insufficient decidualization accompanied by impaired dNK modulation and eventually miscarriage

Zhang,

Xue,

Huang

et al. 2024

J Transl Med

View full text Add to dashboard Cite

Background Miscarriage is a frustrating complication of pregnancy that is common among women of reproductive age. Insufficient decidualization which not only impairs embryo implantation but disturbs fetomaternal immune-tolerance, has been widely regarded as a major cause of miscarriage; however, the underlying mechanisms resulting in decidual impairment are largely unknown. Methods With informed consent, decidual tissue from patients with spontaneous abortion or normal pregnant women was collected to detect the expression profile of UCHL1. Human endometrial stromal cells (HESCs) were used to explore the roles of UCHL1 in decidualization and dNK modulation, as well as the mechanisms involved. C57/BL6 female mice (7–10 weeks old) were used to construct pregnancy model or artificially induced decidualization model to evaluate the effect of UCHL1 on mice decidualization and pregnancy outcome. Results The Ubiquitin C-terminal hydrolase L1 (UCHL1), as a deubiquitinating enzyme, was significantly downregulated in decidua from patients with miscarriage, along with impaired decidualization and decreased dNKs. Blockage of UCHL1 led to insufficient decidualization and resultant decreased expression of cytokines CXCL12, IL-15, TGF-β which were critical for generation of decidual NK cells (dNKs), whereas UCHL1 overexpression enhanced decidualization accompanied by increase in dNKs. Mechanistically, the promotion of UCHL1 on decidualization was dependent on its deubiquitinating activity, and intervention of UCHL1 inhibited the activation of JAK2/STAT3 signaling pathway, resulting in aberrant decidualization and decreased production of cytokines associated with dNKs modulation. Furthermore, we found that inhibition of UCHL1 also disrupted the decidualization in mice and eventually caused adverse pregnancy outcome. Conclusions UCHL1 plays significant roles in decidualization and dNKs modulation during pregnancy in both humans and mice. Its deficiency indicates a poor pregnancy outcome due to defective decidualization, making UCHL1 a potential target for the diagnosis and treatment of miscarriage. Graphical Abstract

show abstract

Ubiquitin C‐terminal hydrolase L1 (UCHL1), a double‐edged sword in mammalian oocyte maturation and spermatogenesis

Cited by 11 publications

References 118 publications

Subtypes analysis and prognostic model construction based on lysosome-related genes in colon adenocarcinoma

Subtypes analysis and prognostic model construction based on lysosome-related genes in colon adenocarcinoma

UCHL1 maintains microenvironmental homeostasis in goat germline stem cells

Deficiency of UCHL1 results in insufficient decidualization accompanied by impaired dNK modulation and eventually miscarriage

Contact Info

Product

Resources

About