ZIYU LIU^1,2, AKIKO OKANO^3,4, EMIKO SANADA^1,3,4, YUSHI FUTAMURA^3,4, TOSHIHIKO NOGAWA^3,5, KOSUKE ISHIKAWA⁶, KENTARO SEMBA^7,8, JIANG LI⁹, XIAOMENG LI¹⁰, HIROYUKI OSADA^3,4,11,*, NOBUMOTO WATANABE^1,2,4,*

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 of cytovaricin and had… More > Graphic Abstract

XINTONG LIU^1,2,3, EMIKO SANADA^1,3,4, JIANG LI⁵, XIAOMENG LI⁶, HIROYUKI OSADA^1,4,7,*, NOBUMOTO WATANABE^1,2,3,*

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 SCF^β-TrCP1 and on downstream signaling pathways were examined. Hit compounds NPD5943, NPL62020-01, and NPL42040-01 inhibited the TNFα-induced degradation of… More > Graphic Abstract

YUSEN ZHANG^1,2,3, LIPING LIU^1,2,3, BIWEI LUO^1,2,3, HONGGUI TANG^1,2,3, XIAOFANG YU^1,2,3, SHIYUN BAO^1,2,3,*

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 on… More >

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 in muscle mass. The pathogenesis… More >

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 proliferator-activated receptor alpha (PPAR )… More >

Hao Luo^1,#,*, Yanjie Ji^2,#, Xinrong Gao¹, Xinying Liu¹, Yunzhao Wu³, Yingli Wu^3,*

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 glioma, testicular cancer, breast cancer,… More >

JIANMIN PAN¹, XIN LI¹, JUANJUAN LI¹, HUI LIU², ZHUONI HOU¹, ZONGQI YANG¹, LING XU^1,*

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… More >

YAO XU^1,#, BIN WU^2,#, JING YANG³, SHENG ZHANG², LONGGEN LIU⁴, SUOBAO XU^2,*, JIAKAI JIANG^2,*

BIOCELL, Vol.46, No.6, pp. 1483-1491, 2022, DOI:10.32604/biocell.2022.017745

Abstract To study the roles and association of murine double minute gene 2 (MDM2) and fructose-1,6-biphosphatase (FBP1) in human hepatocellular carcinoma (HCC), growth response of human HCC cells was assessed using proliferation and apoptosis assay. Pro-survival AKT signaling associated proteins (p-AKT, survivin and cleaved caspase 3) were assessed using western blotting. The correlation between MDM2 and FBP1 was assessed using co-immunoprecipitation combined with ubiquitination assay. Our data suggested that low expression of FBP1 was correlated with high levels of MDM2 in HCC cell lines (Huh7 and Hep3B). Overexpression of FBP1 resulted in anti-proliferation, pro-apoptosis, the up-regulation of cleaved caspase 3 while… More >

SUYING PU^1,#, HUI ZHENG^2,#, YUN TAO¹, JING SHAO¹, MINGNA YANG¹, SHUNJUN LI^1,*

BIOCELL, Vol.46, No.6, pp. 1545-1555, 2022, DOI:10.32604/biocell.2022.017544

Abstract Intracerebral hemorrhage (ICH) is the most serious type of stroke. High level of thrombin is found in the ICH. Ubiquitin-specific protease (USP) 31, a member of deubiquitinating enzymes family, has been found to negatively regulate the NF-κB pathway. However, the function of USP31 in ICH remains largely unknown. In the present study, the mRNA and protein expression levels of USP31 were measured by real-time PCR and western blot. Flow cytometry was used to measure cell apoptosis and the level of reactive oxygen species (ROS). In the current study, we found the mRNA level of USP31 was decreased in peripheral blood… More >

FUJI YANG¹, YAN HUANG¹, YOUWEN TAN^2,*, YONGMIN YAN^1,*

BIOCELL, Vol.46, No.2, pp. 389-400, 2022, DOI:10.32604/biocell.2021.015899

Abstract Nonalcoholic fatty liver disease (NAFLD) is a long-lasting condition that affects the liver, destroying its function. Liver injury can cause steatosis and inflammation, and further activation of hepatic stellate cells (HSCs) often leads to the development of nonalcoholic liver fibrosis. The patient with NAFLD is at risk of developing advanced liver disease and complications, such as liver failure, hepatocellular carcinoma (HCC), and portal hypertension. Although our understanding of the cellular and molecular mechanisms of NAFLD has greatly improved in recent years, treatment remains limited. Analysis and characterization of protein posttranslational modifications (PTMs) could improve our understanding of NAFLD pathology and… More >