USP7 Inhibitors in Cancer Immunotherapy: Current Status and Perspective

Korenev, Georgiy; Yakukhnov, Sergey; Druk, Anastasia; Головина, А. М.; Chasov, Vitaly; Mirgayazova, Regina; Ivanov, Roman; Bulatov, Emil

doi:10.3390/cancers14225539

Cited by 17 publications

(9 citation statements)

References 95 publications

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“…Therefore, components in the ubiquitin pathway have been proposed as potential targets for treatment strategies for diseases and cancer ( 37 , 38 ). USP7 is one of the most abundant USPs and plays a multifaceted role in many cellular events, including carcinogenic pathways ( 39 - 42 ). A study has found that USP7 is a promising target for cancer treatment by regulating the MDM2/MDX-p53 pathway ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

TMEM43 promotes the development of hepatocellular carcinoma by activating VDAC1 through USP7 deubiquitination

Zhang,

Wang,

Yang

et al. 2024

Transl Gastroenterol Hepatol

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Background Transmembrane protein 43 ( TMEM43 ), a member of the TMEM subfamily, is encoded by a highly conserved gene and widely expressed in most species from bacteria to humans. In previous studies, TMEM43 has been found to play an important role in a variety of tumors. However, the role of TMEM43 in cancer remains unclear. Methods We utilized the RNA sequencing (RNA-seq) and The Cancer Genome Atlas (TGCA) databases to explore and identify genes that may play an important role in the occurrence and development of hepatocellular carcinoma (HCC), such as TMEM43 . The role of TMEM43 in HCC was explored through Cell Counting Kit-8 (CCK-8) cloning, flow cytometry, and Transwell experiments. The regulatory relationship between TMEM43 and voltage-dependent anion channel 1 ( VDAC1 ) was investigated through coimmunoprecipitation (co-IP) and western blot (WB) experiments. WB was used to study the deubiquitination effect of ubiquitin-specific protease 7 ( USP7 ) on TMEM43 . Results In this study, we utilized the RNA-seq and TGCA databases to mine data and found that TMEM43 is highly expressed in HCC. The absence of TMEM43 in cancer cells was shown to inhibit tumor development. Further research detected an important regulatory relationship between TMEM43 and VDAC1 . In addition, we found that USP7 affected the progression of HCC by regulating the ubiquitination level of TMEM43 through deubiquitination. Conclusions Our study demonstrated that USP7 participates in the growth of HCC tumors through TMEM43/VDAC1 .Our results suggest that USP7/TMEM43/VDAC1 may have predictive value and represent a new treatment strategy for HCC.

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Section: Discussionmentioning

confidence: 99%

TMEM43 promotes the development of hepatocellular carcinoma by activating VDAC1 through USP7 deubiquitination

Zhang,

Wang,

Yang

et al. 2024

Transl Gastroenterol Hepatol

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“…After nine months of immunotherapy, these correlations changed dramatically, and all symptoms for those patients with a complete response were alleviated almost completely. It is known that cancer-related fatigue is a common symptom, and its prevalence reaches 80 to 90% of cancer patients under treatment [ 31 , 32 ]. Fatigue symptoms are often under-diagnosed and under-treated by health care practitioners.…”

Section: Discussionmentioning

confidence: 99%

Non-Small-Cell Lung Cancer Immunotherapy and Sleep Characteristics: The Crossroad for Optimal Survival

et al. 2023

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Introduction: Non-small-cell lung cancer is still diagnosed at an inoperable stage and systematic treatment is the only option. Immunotherapy is currently considered to be the tip of the arrow as the first-line treatment for patients with a programmed death-ligand 1 ≥ 50. Sleep is known to be an essential part of our everyday life. Patients and Methods: We investigated, upon diagnosis and after nine months, 49 non-small-cell lung cancer patients undergoing immunotherapy treatment with nivolumab and pemprolisumab. A polysomnographic examination was conducted. Moreover, the patients completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI), the Fatigue Severity Scale (FSS) and the Medical Research Council (MRC) dyspnea scale. Results: Tukey mean-difference plots, summary statistics, and the results of paired t-test of five questionnaire responses in accordance with the PD-L1 test across groups were examined. The results indicated that, upon diagnosis, patients had sleep disturbances which were not associated with brain metastases or their PD-L1 expression status. However, the PD-L1 status and disease control were strongly associated, since a PD-L1 ≥80 improved the disease status within the first 4 months. All data from the sleep questionnaires and polysomnography reports indicated that the majority of patients with a partial response and complete response had their initial sleep disturbances improved. There was no connection between nivolumab or pembrolisumab and sleep disturbances. Conclusion: Upon diagnosis, lung cancer patients have sleep disorders such as anxiety, early morning wakening, late sleep onset, prolonged nocturnal waking periods, daytime sleepiness, and unrefreshing sleep. However, these symptoms tend to improve very quickly for patients with a PD-L1 expression ≥80, because disease status improves also very quickly within the first 4 months of treatment.

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“…Further studies are necessary to elucidate the detailed localization and extracellular functions of the ubiquitin-conjugating enzyme complex, including E1, E2, and E3, during fertilization of the ascidian H. roretzi. Although genome editing experiments of E1, E2, and E3 would be difficult due to the inability of culturing a juvenile into a sexually matured adult in an aquarium, several specific inhibitors against the UPS [ 33 ], including deubiquitinating enzyme [ 34 , 35 ], may give us an answer to the questions remained to be solved.…”

Section: Discussionmentioning

confidence: 99%

Involvement in Fertilization and Expression of Gamete Ubiquitin-Activating Enzymes UBA1 and UBA6 in the Ascidian Halocynthia roretzi

Sawada

Inoue

Saitô

et al. 2023

IJMS

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The extracellular ubiquitin–proteasome system is involved in sperm binding to and/or penetration of the vitelline coat (VC), a proteinaceous egg coat, during fertilization of the ascidian (Urochordata) Halocynthia roretzi. It is also known that the sperm receptor on the VC, HrVC70, is ubiquitinated and degraded by the sperm proteasome during the sperm penetration of the VC and that a 700-kDa ubiquitin-conjugating enzyme complex is released upon sperm activation on the VC, which is designated the “sperm reaction”. However, the de novo function of ubiquitin-activating enzyme (UBA/E1) during fertilization is poorly understood. Here, we show that PYR-41, a UBA inhibitor, strongly inhibited the fertilization of H. roretzi. cDNA cloning of UBA1 and UBA6 from H. roretzi gonads was carried out, and their 3D protein structures were predicted to be very similar to those of human UBA1 and UBA6, respectively, based on AlphaFold2. These two genes were transcribed in the ovary and testis and other organs, among which the expression of both was highest in the ovary. Immunocytochemistry showed that these enzymes are localized on the sperm head around a mitochondrial region and the follicle cells surrounding the VC. These results led us to propose that HrUBA1, HrUBA6, or both in the sperm head mitochondrial region and follicle cells may be involved in the ubiquitination of HrVC70, which is responsible for the fertilization of H. roretzi.

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USP7 Inhibitors in Cancer Immunotherapy: Current Status and Perspective

Cited by 17 publications

References 95 publications

TMEM43 promotes the development of hepatocellular carcinoma by activating VDAC1 through USP7 deubiquitination

TMEM43 promotes the development of hepatocellular carcinoma by activating VDAC1 through USP7 deubiquitination

Non-Small-Cell Lung Cancer Immunotherapy and Sleep Characteristics: The Crossroad for Optimal Survival

Involvement in Fertilization and Expression of Gamete Ubiquitin-Activating Enzymes UBA1 and UBA6 in the Ascidian Halocynthia roretzi

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