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 30 publications

(21 citation statements)

References 37 publications

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“…[19][20][21] As a member of the USPs family, USP5 can play the role of deubiquitination enzyme by hydrolyzing ubiquitin chain. 24,25 Wang et al 26 found that inhibiting the expression of deubiquitinase USP5 could lead to degradation of c-Maf protein and induce apoptosis of MM cells. 24,25 Wang et al 26 found that inhibiting the expression of deubiquitinase USP5 could lead to degradation of c-Maf protein and induce apoptosis of MM cells.…”

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confidence: 99%

RETRACTED: miR‐125a suppresses malignancy of multiple myeloma by reducing the deubiquitinase USP5

Wu¹,

Zhang²,

Chen³

et al. 2019

J of Cellular Biochemistry

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miR‐125a is a microRNA that is frequently diminished in various human malignancies. However, the mechanism by which impaired miR‐125a promotes cancer growth remains undefined. In this study, we investigated the role of miR‐125a in the proliferation and apoptosis of multiple myeloma (MM). To do this, we used MM tissue samples (from 40 anonymous patients), normal matched control samples, and five MM‐derived cell lines. We also established a mouse model of MM xenograft to explore the effect of overexpression of miR‐125a on the MM growth in vivo. Quantitative real‐time polymerase chain reaction revealed that the miR‐125a expression was broadly reduced in MM tissues and cell lines. The impairment of miR‐125a in MM tissues was functionally relevant because the overexpression of miR‐125a remarkably decreased the cell viability and colony‐forming activity, at least in part, by promoting apoptosis in two miR‐125a‐deficient MM cell lines: NCI‐H929 and U266. Interestingly, we also discovered that the human gene encoding the ubiquitin‐specific peptidase 5 (USP5), which is known to promote cellular deubiquitination and ubiquitin/proteasome‐dependent proteolysis, was a direct transcriptional target for miR‐125a to repress. More importantly, the heterologous expression of USP5 significantly reversed the growth‐inhibitory effects of miR‐125a on MM cells in vitro. In the mouse xenograft model, overexpressed miR‐125a prominently inhibited the growth of MM tumors and concomitantly reduced the expression of USP5 in tumor tissues. These results suggest that miR‐125a inhibits the expression of USP5, thereby mitigating the proliferation and survival of malignant MM cells. We propose that USP5 acts as an oncoprotein in miR‐125a‐missing cancers.

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confidence: 99%

RETRACTED: miR‐125a suppresses malignancy of multiple myeloma by reducing the deubiquitinase USP5

Wu¹,

Zhang²,

Chen³

et al. 2019

J of Cellular Biochemistry

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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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“…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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Usp5 functions as an oncogene for stimulating tumorigenesis in hepatocellular carcinoma

Cited by 30 publications

References 37 publications

RETRACTED: miR‐125a suppresses malignancy of multiple myeloma by reducing the deubiquitinase USP5

RETRACTED: miR‐125a suppresses malignancy of multiple myeloma by reducing the deubiquitinase USP5

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

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