USP7 regulates HMOX-1 via deubiquitination to suppress ferroptosis and ameliorate spinal cord injury in rats

Wang, Changsheng; Zhu, Yichao; Zhu, Xitian; Chen, Rongsheng; Zhang, Xiaobo; Lian, Nancheng

doi:10.1016/j.neuint.2023.105554

Cited by 6 publications

(4 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 40 ] A study on spinal cord injury associated downregulated USP7 and upregulated HMOX‐1 with improved motor function recovery and ferroptosis prevention. [ 41 ] These findings collectively emphasize the critical regulatory influence of USP7 in ferroptosis across various pathological conditions, presenting potential therapeutic avenues. However, the specific role of USP7 in regulating ferroptosis in GC requires further exploration.…”

Section: Discussionmentioning

confidence: 85%

Blocking Ubiquitin‐Specific Protease 7 Induces Ferroptosis in Gastric Cancer via Targeting Stearoyl‐CoA Desaturase

Guan,

Wang,

et al. 2024

Advanced Science

View full text Add to dashboard Cite

Gastric cancer (GC) presents a formidable global health challenge, and conventional therapies face efficacy limitations. Ubiquitin‐specific protease 7 (USP7) plays pivotal roles in GC development, immune response, and chemo‐resistance, making it a promising target. Various USP7 inhibitors have shown selectivity and efficacy in preclinical studies. However, the mechanistic role of USP7 has not been fully elucidated, and currently, no USP7 inhibitors have been approved for clinical use. In this study, DHPO is identified as a potent USP7 inhibitor for GC treatment through in silico screening. DHPO demonstrates significant anti‐tumor activity in vitro, inhibiting cell viability and clonogenic ability, and preventing tumor migration and invasion. In vivo studies using orthotopic gastric tumor mouse models validate DHPO's efficacy in suppressing tumor growth and metastasis without significant toxicity. Mechanistically, DHPO inhibition triggers ferroptosis, evidenced by mitochondrial alterations, lipid Reactive Oxygen Species (ROS), Malondialdehyde (MDA) accumulation, and iron overload. Further investigations unveil USP7's regulation of Stearoyl‐CoA Desaturase (SCD) through deubiquitination, linking USP7 inhibition to SCD degradation and ferroptosis induction. Overall, this study identifies USP7 as a key player in ferroptosis of GC, elucidates DHPO's inhibitory mechanisms, and highlights its potential for GC treatment by inducing ferroptosis through SCD regulation.

show abstract

Section: Discussionmentioning

confidence: 85%

Blocking Ubiquitin‐Specific Protease 7 Induces Ferroptosis in Gastric Cancer via Targeting Stearoyl‐CoA Desaturase

Guan,

Wang,

et al. 2024

Advanced Science

View full text Add to dashboard Cite

show abstract

“…Our analysis here indicates that redox regulation is impaired, however, the mechanisms for this are unclear. Several of the proteins we have identified as decreased in the K6W-Ub lenses are known to be regulated by the ubiquitin proteasome pathway, including HMOX1 and GSTP1 [ 51 , 79 ]. Additionally, the rate limiting enzyme for taurine synthesis, cysteine dioxygenase (CDO1) is also regulated by the ubiquitin proteasome system [ 80 ].…”

Section: Discussionmentioning

confidence: 99%

Unbalanced redox status network as an early pathological event in congenital cataracts

Bejarano,

Whitcomb,

Pfeiffer

et al. 2023

Redox Biology

View full text Add to dashboard Cite

“…USP7 overexpression alleviates SCI through facilitating the expression of HMOX-1 through deubiquitination, thereby reducing ferroptosis. 366 MS Methylation GPX4 The histone methyltransferase G9a promotes neurodegeneration through inducing ferroptosis via catalyzing the repressive mark H3K9me2 that suppresses the expression of GCLC, CBS, and GPX4. 378 MS ncRNA EZH2/SLC7A11 BMSC-Exos containing miR-367-3p attenuates the severity of EAE through suppressing ferroptosis via restraining EZH2 expression, leading to the overexpression of SLC7A11.…”

Section: Epigenetic and Posttranslational Modifications Regulating Fe...mentioning

confidence: 99%

“…USP7 overexpression alleviates SCI through deubiquitination of HMOX-1 and promotion of its expression, thereby reducing ferroptosis. 366 …”

Section: Epigenetic and Posttranslational Modifications Regulating Fe...mentioning

confidence: 99%

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Wang,

Hu,

et al. 2023

Sig Transduct Target Ther

View full text Add to dashboard Cite

Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other cell death modes, plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications and posttranslational modifications (PTMs) promote anticancer drug resistance, cancer progression, and metastasis. Accumulating studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases (NSDs), cardiovascular diseases (CVDs), liver diseases, lung diseases, and kidney diseases. In this review, we first summarize the core molecular mechanisms of ferroptosis. Then, the roles of epigenetic processes, including histone PTMs, DNA methylation, and noncoding RNA regulation and PTMs, such as phosphorylation, ubiquitination, SUMOylation, acetylation, methylation, and ADP-ribosylation, are concisely discussed. The roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases, including cancers, NSD, CVDs, liver diseases, lung diseases, and kidney diseases, as well as the application of epigenetic and PTM modulators in the therapy of these diseases, are then discussed in detail. Elucidating the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other diseases. In addition, these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases.

show abstract

USP7 regulates HMOX-1 via deubiquitination to suppress ferroptosis and ameliorate spinal cord injury in rats

Cited by 6 publications

References 34 publications

Blocking Ubiquitin‐Specific Protease 7 Induces Ferroptosis in Gastric Cancer via Targeting Stearoyl‐CoA Desaturase

Blocking Ubiquitin‐Specific Protease 7 Induces Ferroptosis in Gastric Cancer via Targeting Stearoyl‐CoA Desaturase

Unbalanced redox status network as an early pathological event in congenital cataracts

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

Contact Info

Product

Resources

About