Knockdown of Ubiquitin-Specific Protease 53 Enhances the Radiosensitivity of Human Cervical Squamous Cell Carcinoma by Regulating DNA Damage-Binding Protein 2

Zhou, Qifen; Yao, Xiongbo; Wu, Chunlin; Chen, Shaohua; Fan, Dage

doi:10.1177/1533033820929792

Cited by 14 publications

(11 citation statements)

References 21 publications

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“…In addition, FBXO21 belongs to F-box proteins which serves as the substrate-recognition subunit of a SKP1-CUL1-F-box protein (SCF)-type ubiquitin ligase (Watanabe, Yumimoto, & Nakayama, 2015), and ubiquitin-specific proteases 53 (USP53) belongs to the family of deubiquitinating enzymes, which catalyze the reversible modification of target proteins with ubiquitin and stabilize proteins (Fraile, Quesada, Rodriguez, Freije, & Lopez-Otin, 2012). It has been reported that knockdown of USP53 in Siha cells downregulated damage-specific DNA binding protein and caused G2/M cell cycle arrest and decreased the survival rate of cells in response to radiation (Zhou, Yao, Wu, Chen, & Fan, 2020). However, little has been reported about the role of FBXO21 and USP53 in AML.…”

Section: Discussionmentioning

confidence: 99%

RNA sequencing analyses of gene expression by CRISPR/Cas9 knockout of CLL-1 gene in acute myeloid leukemia cells

Fang

Jun

et al. 2022

Preprint

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CLL-1 has been revealed its potential role in acute myeloid leukemia (AML), however, the underlying mechanisms remain unclear. CRISPR/Cas9 strategy was employed to knock out CLL-1 gene in U937 cells and western-blot was used to validate the success of knock out. CCK8 and Transwell assays were used to detect cells viability and migration, respectively. RNA-sequencing was performed to profile mRNA expression in CLL-1 gene knock-out and wide type U937 cells. A cutoff of 1.5-fold change and false discovery rate (FDR)<0.05 was used to screen differentially expressed genes (DEGs), which were presented by volcano plots and hierarchical cluster heatmap. Protein-protein interaction (PPI) network was constructed by String database and Cytoscape software. Furthermore, hub genes were mined by CytoNCA and MCODE, which were subjected to functional enrichment using R package. Finally, the findings were validated using qRT-PCR and western-blot. The protein level of CLL-1 was significantly lowered, and cell viability and migration were suppressed in knock-out cells compared to wide type. Using RNA-sequencing and bioinformatics analysis, 452 DEGs (179 up-regulated and 273 down-regulated) were obtained, and several important hub genes (such as CCR2, FBXO21, UBB and UBE2C) were filtered out, which were enriched in 132 GO terms and 36 KEGG pathways such as chemokine signaling pathway and ubiquitin mediated proteolysis. A total of 8 representative genes mRNA expressions were validated by qRT-PCR, and the protein levels of 6 genes were confirmed by western-blot. CLL-1 gene might exert its role in AML through modulating genes enriched in multiple functions such as chemokine signaling and ubiquitination. Our results may give us new knowledge of CLL-1 in AML and provide a basis for mining novel targets.

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Section: Discussionmentioning

confidence: 99%

RNA sequencing analyses of gene expression by CRISPR/Cas9 knockout of CLL-1 gene in acute myeloid leukemia cells

Fang

Jun

et al. 2022

Preprint

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“…Recently, USP34 has been reported as a positive regulator in osteogenic differentiation of hBMSCs 36 . Additionally, in the study about USP53, it was overexpressed in cervical cancer tissues and the inhibition of USP53 reduced cancer cell arrest 37 . But, none of the studies has reported about deubiquitinase enzyme which is related to osteoporosis.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-specific protease 53 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

et al. 2021

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The ubiquitin protease pathway plays important role in human bone marrow-derived mesenchymal stem cell (hBMSC) differentiation, including osteogenesis. However, the function of deubiquitinating enzymes in osteogenic differentiation of hBMSCs remains poorly understood. In this study, we aimed to investigate the role of ubiquitin-specific protease 53 (USP53) in the osteogenic differentiation of hBMSCs. Based on re-analysis of the Gene Expression Omnibus database, USP53 was selected as a positive regulator of osteogenic differentiation in hBMSCs. Overexpression of USP53 by lentivirus enhanced osteogenesis in hBMSCs, whereas knockdown of USP53 by lentivirus inhibited osteogenesis in hBMSCs. In addition, USP53 overexpression increased the level of active β-catenin and enhanced the osteogenic differentiation of hBMSCs. This effect was reversed by the Wnt/β-catenin inhibitor DKK1. Mass spectrometry showed that USP53 interacted with F-box only protein 31 (FBXO31) to promote proteasomal degradation of β-catenin. Inhibition of the osteogenic differentiation of hBMSCs by FBXO31 was partially rescued by USP53 overexpression. Animal studies showed that hBMSCs with USP53 overexpression significantly promoted bone regeneration in mice with calvarial defects. These results suggested that USP53 may be a target for gene therapy for bone regeneration.

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“…Changes in USP53 cause instability of tight junctions in the hepatocytes [ 17 , 22 , 92 ]. USP53 gene has been associated with some models of tumorigenesis: In clear cell renal cell carcinoma inhibits the occurrence and development of cancer through NF-κB pathway inactivation [ 93 ]; In cervical squamous cell carcinoma correlated with the sensitivity to radiotherapy [ 94 ]; In oesophagal carcinoma, USP53 suppresses cancer progression by regulating cell growth and metabolism [ 95 ]; In lung adenocarcinoma, USP53 regulates cell apoptosis and glycolysis through the AKT1 pathway acting as a tumour suppressor [ 96 ]. …”

Section: Progressive Familial Intrahepatic Cholestasis-related Genesmentioning

confidence: 99%

Genetics in Familial Intrahepatic Cholestasis: Clinical Patterns and Development of Liver and Biliary Cancers: A Review of the Literature

Vitale

Mattiaccio

Conti

et al. 2022

Cancers

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The family of inherited intrahepatic cholestasis includes autosomal recessive cholestatic rare diseases of childhood involved in bile acids secretion or bile transport defects. Specific genetic pathways potentially cause many otherwise unexplained cholestasis or hepatobiliary tumours in a healthy liver. Lately, next-generation sequencing and whole-exome sequencing have improved the diagnostic procedures of familial intrahepatic cholestasis (FIC), as well as the discovery of several genes responsible for FIC. Moreover, mutations in these genes, even in the heterozygous status, may be responsible for cryptogenic cholestasis in both young and adults. Mutations in FIC genes can influence serum and hepatic levels of bile acids. Experimental studies on the NR1H4 gene have shown that high bile acids concentrations cause excessive production of inflammatory cytokines, resistance to apoptosis, and increased cell regeneration, all risk conditions for developing hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). NR1H4 gene encodes farnesoid X-activated receptor having a pivotal role in bile salts synthesis. Moreover, HCC and CCA can emerge in patients with several FIC genes such as ABCB11, ABCB4 and TJP2. Herein, we reviewed the available data on FIC-related hepatobiliary cancers, reporting on genetics to the pathophysiology, the risk factors and the clinical presentation.

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Knockdown of Ubiquitin-Specific Protease 53 Enhances the Radiosensitivity of Human Cervical Squamous Cell Carcinoma by Regulating DNA Damage-Binding Protein 2

Cited by 14 publications

References 21 publications

RNA sequencing analyses of gene expression by CRISPR/Cas9 knockout of CLL-1 gene in acute myeloid leukemia cells

RNA sequencing analyses of gene expression by CRISPR/Cas9 knockout of CLL-1 gene in acute myeloid leukemia cells

Ubiquitin-specific protease 53 promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells

Genetics in Familial Intrahepatic Cholestasis: Clinical Patterns and Development of Liver and Biliary Cancers: A Review of the Literature

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