Usp5 functions as an oncogene for stimulating tumorigenesis in hepatocellular carcinoma

Liu, Yi; Wang, Wei-Mao; Lu, Yuan-Qiang; Lu, Feng; Li, Li; Pan, Mingzhu; Sun, Yu; Suen, Chun-wai; Guo, Wei; Pang, Jianxin; Zhang, Jinfang; Fu, Weiming

doi:10.18632/oncotarget.16901

Cited by 28 publications

(19 citation statements)

References 37 publications

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“…Hepatocellular carcinoma (HCC), the most common primary malignant liver cancer, is a global public health problem that accounts for approximately 500,000 deaths annually [ 1 ]. The high recurrence and low 5-year survival rate of HCC are mainly due to the intrahepatic and extrahepatic metastases [ 2 ], and the rate of recurrence is 86.5% for intrahepatic metastasis and 13.5% for extrahepatic metastasis [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-10b regulates epithelial–mesenchymal transition by modulating KLF4/KLF11/Smads in hepatocellular carcinoma

Hujie

Zhou²,

Zhang

et al. 2018

Cancer Cell Int

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BackgroundOur previous work showed that miR-10b was overexpressed in hepatocellular carcinoma (HCC) and promoted HCC cell migration and invasion. Epithelial–mesenchymal transition (EMT) is involved in HCC metastasis. So, we suspected that miR-10b might participate in the HCC EMT.MethodsWe performed morphological analysis and immunofluorescence to observe the roles of miR-10b in HCC EMT. The expression of KLF11 and EMT markers were detected by real-time RT-PCR and western blot. The regulation roles of miR-10b on KLF11 and KLF4 were determined by luciferase reporter assay. The chromatin immunoprecipitation revealed the binding relationship between KLF4 and KLF11.ResultsWe found that overexpression of miR-10b could promote HCC EMT. miR-10b could upregulated KLF11 expression. The upregulation of KLF11 reduced the downstream molecular Smad7 expression, which upregulated the Smad3 expression to promote EMT development. Furthermore, the induction role of miR-10b in HCC EMT could be blocked by KLF11 siRNA. But our results showed that there was no direct regulation of miR-10b in KLF11 expression. Specifically, miR-10b could bind to the 3′UTR of KLF4 and inhibit KLF4 expression. KLF4 could directly bind to KLF11 promoter and downregulate KLF11 transcription.ConclusionOur results reveal that miR-10b downregulates KLF4, the inhibitory transcriptional factor of KLF11, which induces Smads signaling activity to promote HCC EMT. Our study presents the regulation mechanism of miR-10b in EMT through the KLF4/KLF11/Smads pathway for the first time and implicates miR-10b as a potential target for HCC therapies.

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Section: Introductionmentioning

confidence: 99%

MicroRNA-10b regulates epithelial–mesenchymal transition by modulating KLF4/KLF11/Smads in hepatocellular carcinoma

Hujie

Zhou²,

Zhang

et al. 2018

Cancer Cell Int

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“…USP5 , namely ubiquitin specific peptidase 5, plays an important role in ubiquitination. USP5 expression has been proven to be associated with several cancer types, such as hepatocellular carcinoma, glioblastoma and pancreatic cancer . Previous studies have shown that USP5 had many cellular targets and stabilizes multiple proteins, such as p53 .…”

Section: Discussionmentioning

confidence: 99%

“…USP5 expression has been proven to be associated with several cancer types, such as hepatocellular carcinoma, glioblastoma and pancreatic cancer. [39][40][41] Previous studies have shown that USP5 had many cellular targets and stabilizes multiple proteins, such as p53. 42 TPI1, triosephosphate isomerase 1, encodes a crucial enzyme in the carbohydrate metabolism, and previous studies have shown its expression level might be associated with several cancer types.…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk

Dai

Huang

Amos³

et al. 2019

Intl Journal of Cancer

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Genome‐wide association studies (GWAS) have identified 45 susceptibility loci associated with lung cancer. Only less than SNPs, small insertions and deletions (INDELs) are the second most abundant genetic polymorphisms in the human genome. INDELs are highly associated with multiple human diseases, including lung cancer. However, limited studies with large‐scale samples have been available to systematically evaluate the effects of INDELs on lung cancer risk. Here, we performed a large‐scale meta‐analysis to evaluate INDELs and their risk for lung cancer in 23,202 cases and 19,048 controls. Functional annotations were performed to further explore the potential function of lung cancer risk INDELs. Conditional analysis was used to clarify the relationship between INDELs and SNPs. Four new risk loci were identified in genome‐wide INDEL analysis (1p13.2: rs5777156, Insertion, OR = 0.92, p = 9.10 × 10−8; 4q28.2: rs58404727, Deletion, OR = 1.19, p = 5.25 × 10−7; 12p13.31: rs71450133, Deletion, OR = 1.09, p = 8.83 × 10−7; and 14q22.3: rs34057993, Deletion, OR = 0.90, p = 7.64 × 10−8). The eQTL analysis and functional annotation suggested that INDELs might affect lung cancer susceptibility by regulating the expression of target genes. After conducting conditional analysis on potential causal SNPs, the INDELs in the new loci were still nominally significant. Our findings indicate that INDELs could be potentially functional genetic variants for lung cancer risk. Further functional experiments are needed to better understand INDEL mechanisms in carcinogenesis.

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“…Ubiquitin-specific protease 5 (USP5) belongs to the ubiquitin-specific protease (USP) family, and it has been identified as a tumor promoter in several types of human cancer. Increased ubiquitin-specific protease 5 (USP5) has been associated with tumorigenesis of malignancy including pancreatic cancer, melanoma, non-small-cell lung cancer, and hepatocellular carcinoma [11][12][13]. Recent study also showed that USP5 is essential for the production of TNF-α in mucosal mast cells [14].…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Luo

Liu

et al. 2020

Mediators of Inflammation

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Rheumatoid arthritis (RA) is a worldwide chronic autoimmune inflammatory disease which is affecting approximately 1% of the total population. It is characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS) and increased production of proinflammatory cytokines. In the current study, we were aiming to investigate the role of ubiquitin-specific protease 5 (USP5) in the inflammatory process in RA-FLS. Expression of USP5 was found upregulated in RA-FLS compared with that in osteoarthritis- (OA-) FLS, and IL-1β stimulation increased USP5 expression in a time-dependent manner. Furthermore, we found that USP5 overexpression significantly aggravated proinflammatory cytokine production and related nuclear factor κB (NF-κB) signaling activation. Consistently, silencing of USP5 decreased the release of cytokines and inhibited the activation of NF-κB. In addition, USP5 was found to interact with tumor necrosis factor receptor-associated factor 6 (TRAF6) and remove its K48-linked polyubiquitination chains therefore stabilizing TRAF6. Our data showed that a USP5-positive cell regulates inflammatory processes in RA-FLS and suggested USP5 as a potential target for RA treatment.

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Usp5 functions as an oncogene for stimulating tumorigenesis in hepatocellular carcinoma

Cited by 28 publications

References 37 publications

MicroRNA-10b regulates epithelial–mesenchymal transition by modulating KLF4/KLF11/Smads in hepatocellular carcinoma

MicroRNA-10b regulates epithelial–mesenchymal transition by modulating KLF4/KLF11/Smads in hepatocellular carcinoma

Genome‐wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk

Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

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