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Search Results (15)
  • Open Access

    ARTICLE

    E3 ubiquitin ligase CBL-B suppresses vascular endothelial cell pyroptosis and injury in intracranial aneurysm by facilitating NLRP3 degradation

    WEI ZHENG1, CHENG LIU2,*

    BIOCELL, Vol.48, No.2, pp. 293-301, 2024, DOI:10.32604/biocell.2023.044211

    Abstract Objective: Intracranial aneurysm (IA) represents a devastating disease with high rates of disability and mortality, which is initiated by dysfunction of endothelial cells (ECs). Evidence suggests the dysregulation of the E3 ubiquitin ligase family during EC injury. In this work, the role of an E3 ubiquitin ligase, casitas B lymphoma-B (CBL-B), was explored in human brain microvascular EC (HBMEC) function through the NLRP3 pathway. Methods: In vitro IA model was induced by treating HBMECs with oxidized low-density lipoprotein (ox-LDL). The levels of CBL-B and pyroptosis-related proteins NLRP3, ASC, cleaved caspase-1, and GSDME-N were determined by real-time-quantitative… More >

  • Open Access

    ARTICLE

    Systematic analysis of DNA polymerases as therapeutic targets in pan-cancers

    ZHENHUA LI1, HUILAI LV1, FAN ZHANG1, ZIMING ZHU2, QIANG GUO3, MINGBO WANG1, CHAO HUANG1, LIJUAN CHEN4, WENPAN ZHANG4, YUN LI5,*, ZIQIANG TIAN1,*

    BIOCELL, Vol.48, No.1, pp. 123-138, 2024, DOI:10.32604/biocell.2023.031568

    Abstract Introduction: DNA polymerases are crucial for maintaining genome stability and influencing tumorigenesis. However, the clinical implications of DNA polymerases in tumorigenesis and their potential as anti-cancer therapy targets are not well understood. Methods: We conducted a systematic analysis using TCGA Pan-Cancer Atlas data and Gene Set Cancer Analysis results to examine the expression profiles of 15 DNA polymerases (POLYs) and their clinical correlations. We also evaluated the prognostic value of POLYs by analyzing their expression levels in relation to overall survival time (OS) using Kaplan-Meier survival curves. Additionally, we investigated the correlations between POLY expression… More >

  • Open Access

    ARTICLE

    UCHL5 inhibits U251 glioma cell proliferation and tumor growth via stabilizing and deubiquitinating PTEN

    YUE XIAO1,2,#, WENJING MA2,#, XINYI CHEN2, WEIWEI HU3, QIANQIAN DI2, XIBAO ZHAO2, GUODONG HUANG1, WEILIN CHEN1,2,*

    BIOCELL, Vol.47, No.12, pp. 2617-2625, 2023, DOI:10.32604/biocell.2023.042476

    Abstract Background: Glioma is the most common primary brain tumor. Exploration of new tumorigenesis mechanism of glioma is critical to determine more effective treatment targets as well as to develop effective prognosis methods that can enhance the treatment efficacy. We previously demonstrated that the deubiquitinase biquitin carboxyl-terminal hydrolase L5 (UCHL5) was downregulated in human glioma. However, the effect and mechanism of UCHL5 on the proliferation of glioma cells remains unknown. Methods: Transfection of siRNA was used to knockdown the expression of UCHL5 in U251 cells. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, Edu assay, and colony formation… More > Graphic Abstract

    UCHL5 inhibits U251 glioma cell proliferation and tumor growth via stabilizing and deubiquitinating PTEN

  • Open Access

    ARTICLE

    Identification of microbial metabolites that accelerate the ubiquitin-dependent degradation of c-Myc

    ZIYU LIU1,2, AKIKO OKANO3,4, EMIKO SANADA1,3,4, YUSHI FUTAMURA3,4, TOSHIHIKO NOGAWA3,5, KOSUKE ISHIKAWA6, KENTARO SEMBA7,8, JIANG LI9, XIAOMENG LI10, HIROYUKI OSADA3,4,11,*, NOBUMOTO WATANABE1,2,4,*

    Oncology Research, Vol.31, No.5, pp. 655-666, 2023, DOI:10.32604/or.2023.030248

    Abstract

    Myc belongs to a family of proto-oncogenes that encode transcription factors. The overexpression of c-Myc causes many types of cancers. Recently, we established a system for screening c-Myc inhibitors and identified antimycin A by screening the RIKEN NPDepo chemical library. The specific mechanism of promoting tumor cell metastasis by high c-Myc expression remains to be explained. In this study, we screened approximately 5,600 microbial extracts using this system and identified a broth prepared from Streptomyces sp. RK19-A0402 strongly inhibits c-Myc transcriptional activity. After purification of the hit broth, we identified compounds closely related to the aglycone

    More > Graphic Abstract

    Identification of microbial metabolites that accelerate the ubiquitin-dependent degradation of c-Myc

  • Open Access

    ARTICLE

    Isolation and characterization of β-transducin repeat-containing protein ligands screened using a high-throughput screening system

    XINTONG LIU1,2,3, EMIKO SANADA1,3,4, JIANG LI5, XIAOMENG LI6, HIROYUKI OSADA1,4,7,*, NOBUMOTO WATANABE1,2,3,*

    Oncology Research, Vol.31, No.5, pp. 645-654, 2023, DOI:10.32604/or.2023.030240

    Abstract β-transducin repeat-containing protein (β-TrCP) is an F-box protein subunit of the E3 Skp1-Cullin-F box (SCF) type ubiquitin-ligase complex, and provides the substrate specificity for the ligase. To find potent ligands of β-TrCP useful for the proteolysis targeting chimera (PROTAC) system using β-TrCP in the future, we developed a high-throughput screening system for small molecule β-TrCP ligands. We screened the chemical library utilizing the system and obtained several hit compounds. The effects of the hit compounds on in vitro ubiquitination activity of SCFβ-TrCP1 and on downstream signaling pathways were examined. Hit compounds NPD5943, NPL62020-01, and NPL42040-01 inhibited the… More > Graphic Abstract

    Isolation and characterization of β-transducin repeat-containing protein ligands screened using a high-throughput screening system

  • Open Access

    ARTICLE

    Calcyclin-binding protein contributes to cholangiocarcinoma progression by inhibiting ubiquitination of MCM2

    YUSEN ZHANG1,2,3, LIPING LIU1,2,3, BIWEI LUO1,2,3, HONGGUI TANG1,2,3, XIAOFANG YU1,2,3, SHIYUN BAO1,2,3,*

    Oncology Research, Vol.31, No.3, pp. 317-331, 2023, DOI:10.32604/or.2023.028418

    Abstract Background: Cholangiocarcinoma (CCA) represents the epithelial cell cancer with high aggressiveness whose five-year survival rate is poor with standard treatment. Calcyclin-binding protein (CACYBP) shows aberrant expression within several malignant tumors, but the role of CACYBP in CCA remains unknown. Methods: Immunohistochemical (IHC) analysis was used to identify CACYBP overexpression in clinical samples of CCA patients. Moreover, its correlation with clinical outcome was revealed. Furthermore, CACYBP’s effect on CCA cell growth and invasion was investigated in vitro and in vivo using loss-of-function experiments. Results: CACYBP showed up-regulation in CCA, which predicts the dismal prognostic outcome. CACYBP had an important effect More >

  • Open Access

    REVIEW

    The role of 5′-adenosine monophosphate-activated protein kinase (AMPK) in skeletal muscle atrophy

    KAI DANG, HAFIZ MUHAMMAD UMER FAROOQ, YUAN GAO, XIAONI DENG, AIRONG QIAN*

    BIOCELL, Vol.47, No.2, pp. 269-281, 2023, DOI:10.32604/biocell.2023.023766

    Abstract As a key coordinator of metabolism, AMP-activated protein kinase (AMPK) is vitally involved in skeletal muscle maintenance. AMPK exerts its cellular effects through its function as a serine/threonine protein kinase by regulating many downstream targets and plays important roles in the development and growth of skeletal muscle. AMPK is activated by phosphorylation and exerts its function as a kinase in many processes, including synthesis and degradation of proteins, mitochondrial biogenesis, glucose uptake, and fatty acid and cholesterol metabolism. Skeletal muscle atrophy is a result of various diseases or disorders and is characterized by a decrease More >

  • Open Access

    ARTICLE

    Tripartite Motif-Containing 46 Promotes Viability and Inhibits Apoptosis of Osteosarcoma Cells by Activating NF-kB Signaling Through Ubiquitination of PPARα

    Wenwei Jiang*, Xinyu Cai*, Tianyang Xu*, Kaiyuan Liu*, Dong Yang*, Lin Fan*, Guodong Li*, Xiao Yu

    Oncology Research, Vol.28, No.4, pp. 409-421, 2020, DOI:10.3727/096504020X15868639303417

    Abstract Osteosarcoma (OS), the most common bone cancer, causes high morbidity in children and young adults. TRIM46 is a member of the family of tripartite motif (TRIM)-containing proteins that serve as important regulators of tumorigenesis. Here we investigate the possible role of TRIM46 in OS and the underlying molecular mechanism. We report an increase in the expression of TRIM46 in OS and its association with tumor size, Enneking’s stage, and patient prognosis. TRIM46 knockdown inhibits OS cell viability and cell cycle progression and induces apoptosis, while TRIM46 overexpression exerts inverse effects, which are inhibited by peroxisome… More >

  • Open Access

    REVIEW

    Ubiquitin Specific Protease 2: Structure, Isoforms, Cellular Function, Related Diseases and Its Inhibitors

    Hao Luo1,#,*, Yanjie Ji2,#, Xinrong Gao1, Xinying Liu1, Yunzhao Wu3, Yingli Wu3,*

    Oncologie, Vol.24, No.1, pp. 85-99, 2022, DOI:10.32604/oncologie.2022.021705

    Abstract The ubiquitin-proteasome system (UPS) is an important pathway for cellular protein degradation. The components of this pathway, including the proteasome, ubiquitinase, and deubiquitinase, are highly specialized and strictly regulated. The ubiquitin-specific protease 2 (USP2) belongs to the ubiquitin-specific proteases, a subgroup of deubiquitinating enzymes. USP2 plays essential roles in regulating cell survival, cell cycle, circadian rhythm, cell metabolism, inflammatory response, antiviral response, and metastasis by interacting with certain proteins such as Cyclin D1, PER1, CRY1, HDM2/p53, FASN, LDLR, TRAF6, TBK1, and TGFBR1-TGFBR2 complex. Elevation of USP2 has been observed in a variety of cancers, including… More >

  • Open Access

    ARTICLE

    Genome-wide identification of U-box gene family and expression analysis under abiotic stresses in Salvia miltiorrhiza

    JIANMIN PAN1, XIN LI1, JUANJUAN LI1, HUI LIU2, ZHUONI HOU1, ZONGQI YANG1, LING XU1,*

    BIOCELL, Vol.46, No.7, pp. 1751-1762, 2022, DOI:10.32604/biocell.2022.019455

    Abstract Plant U-box (PUB) E3 ubiquitin ligases play important roles in hormone signaling pathways and in response to different abiotic stresses, but little is known about U-box genes in Danshen (root of Salvia miltiorrhiza Bunge). Here, we identified and characterized 70 SmPUB genes based on its genome sequence. Phylogenetic analysis of U-box genes from S. miltiorrhiza and Arabidopsis suggested that they can be clustered into seven subgroups (I–VII). Typical U-box domains were found in all identified SmPUB genes through the analysis of conserved motifs. Moreover, qRT-PCR was applied to analyze the relative expression levels of U-box genes in S. miltiorrhiza roots and More >

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