USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma

Lu, Chao; Zhang, Ning; Wang, Aman; Chen, Di; Liu, Xiaolong; Xia, Tian; Tekcham, Dinesh Singh; Wang, Wen; Li, Tongming; Liu, Xiumei; Liu, Jing; Qi, Huan; Luo, Haifeng; Du, Jian; Ma, Chi; Qiu, Yan; Liu, Jiwei; Xu, Guowang; Piao, Hulin; Tan, Guang

doi:10.1016/j.canlet.2018.07.032

Cited by 56 publications

(54 citation statements)

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“…They demonstrated that USP10 inhibits the mTOR signaling pathway to deter cell growth in hepatocellular carcinoma. Further evidence that corroborates our results indicates that USP10 is a tumor suppressor in various cancer types, including gastric cancer [11], hepatocellular carcinoma [15], non-small cell lung cancer [17], small intestinal adenocarcinoma [18], and ovary cancer [25].…”

Section: Discussionsupporting

confidence: 85%

“…In addition, is an important mediator in the c-Myc-USP10-p14ARF axis because it deubiquitinates and stabilizes p14ARF [17]. Lu et al also suggested that USP10 behaves as a tumor suppressor in hepatocellular carcinoma [15].…”

Section: Discussionmentioning

confidence: 99%

“…Among the USPs, ubiquitin-specific proteases 10 (USP 10) is a primary cytoplasmic deubiquitinase that acts as a tumor suppressor gene or oncogene as it regulates different substrates, including p53 [7], AMP-activated protein kinase (AMPK) [8], fms-like tyrosine kinase 3 (FLT3) [9], and phosphatase and tensin homolog (PTEN) [10]. Furthermore, the elevation or loss of USP10 expression has already been linked to poor prognosis in various cancers, including stomach [11], breast [12], prostate [13], glioblastoma [14], hepatocellular [15], and non-small cell lung cancer [16]. Ko et al recently reported that USP10 plays a crucial role in oncogene-induced senescence by regulating the stability of p14ARF and that dual loss of USP10 and p14ARF is a factor indicating an negative outcome in patients with non-small cell lung cancer [17].…”

Section: Introductionmentioning

confidence: 99%

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Decreased expression of ubiquitin-specific protease 10 correlates unfavorable prognosis in colorectal cancer

T²,

Park³

et al. 2020

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Background: Ubiquitin-specific proteases (USPs) play an important role in fundamental cellular processes. Among these, USP10 is known for its association with tumor development and progression of multiple cancers. Here, we found a potential link between USP10 and p14ARF in colorectal cancer.Methods: USP10 and p14ARF protein expression was assessed via immunohistochemistry (IHC) on a tissue microarray from 280 colorectal cancer cases. IHC scores were evaluated by digital image analysis and compared with patients' outcomes. In addition, we examined DNA hypermethylation in colorectal cancer cell lines and tissues, which were matched with adjacent normal colon samples.Results: USP10 expression (USP10 loss ) was lost in 18.6% of samples (52/280 cases), which was linked to lymphovascular invasion ( p =0.019) and distant metastases ( p <0.001). Similarly, loss of p14ARF expression (p14ARF loss ) was associated with more advanced tumors. USP10 expression correlated positively with p14ARF expression ( r =0.617, p <0.001). USP10 loss , p14ARF loss , and loss of both USP10 and p14ARF (USP10 loss /p14ARF loss ) were significantly associated with shorter disease-free survival and overall survival in comparison to USP10 intact , p14ARF intact , and USP10 intact /p14ARF intact , respectively. Multivariate analysis revealed that USP10 loss (Hazard ratio=2.07, p =0.046) and USP10 loss /p14ARF loss (Hazard ratio=1.41, p =0.010) are independent prognostic factors for disease-free survival in colorectal cancer patients. Furthermore, aberrant hypermethylation of the USP10 promoter region was found in colorectal cancer cell lines and tissues.Conclusions: The present results suggest that USP10 loss is a potential prognostic marker for colorectal cancer.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Decreased expression of ubiquitin-specific protease 10 correlates unfavorable prognosis in colorectal cancer

T²,

Park³

et al. 2020

Preprint

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“…Meanwhile, an intact mTORC1 axis [16] and mTORC2-Akt1 cascade [17] were required for c-Myc-driven hepatocarcinogenesis. Moreover, some researches [15,18] provided the theoretical basis of mTOR signaling pathway-oriented targeting treatment for HCC in clinic. Overall, these abovementioned evidences demonstrated that mTOR signal pathway plays an important role in the development of HCC.…”

Section: Discussionmentioning

confidence: 99%

A Novel Signature Based On Mtorc1 Pathway In Hepatocellular Carcinoma

Zhang

2020

Preprint

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BackgroundmTORC1 signal pathway play a role in the initiation and progression of hepatocellular carcinoma (HCC), but no relevant gene signature was developed. This research aimed to explore the potential correlation between mTORC1 signal pathway and HCC and establish the related genes signature.MethodsHCC cases were retrieved from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) databases. The genes to be included in mTORC1-assiociated signature were selected by performing univariate, multivariate Cox regression analysis and lasso regression analysis. Then, the signature was verified by survival analysis and multiple receiver operating characteristic (ROC) curve. Moreover, the correlation between signature and immune cells infiltration was investigated. Furthermore, a nomogram was established and evaluated by C-index and calibration plot.ResultsThe signature was established with the six genes (ETF1, GSR, SKAP2, HSPD1, CACYBP and PNP). Under the grouping from signature, patients in the high- risk group showed worse survival than those in the low-risk group in both three datasets. The signature was found significantly associated with the infiltration of B cells, CD4+T-cells, CD8+T-cells, dendritic cells, macrophages and neutrophils. The univariate and multivariate Cox regression analysis indicated that mTORC1 related signature can be the potential independent prognostic factor in HCC. Finally, the nomogram involved age, gender, stage and signature have been established.ConclusionThe mTORC1 associated gene signature established and validated in our research could be used as a potential prognostic factor in HCC. *These authors contributed equally.

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“…Meanwhile, an intact mTORC1 axis [16] and mTORC2-Akt1 cascade [17] were required for c-Mycdriven hepatocarcinogenesis. Moreover, some researches [15,18] provided the theoretical basis of mTOR signaling pathway-oriented targeting treatment for HCC in clinic. Overall, mTOR signal pathway plays an important role in the development and progression of HCC.…”

Section: Discussionmentioning

confidence: 99%

Idenfication of a novel signature based on mTORC1 pathway for hepatocellular carcinoma.

Mo¹,

Luo²,

Cao³

et al. 2020

Preprint

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Background mTORC1 signal pathway play a role in the initiation and progression of hepatocellular carcinoma (HCC), but no relevant gene signature was developed. This research aimed to explore the potential correlation between mTORC1 signal pathway and HCC and establish the related genes signature. Methods HCC cases were retrieved from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) databases. The genes to be included in mTORC1-assiociated signature were selected by performing univariate, multivariate Cox regression analysis and lasso regression analysis. Then, the signature was verified by survival analysis and multiple receiver operating characteristic (ROC) curve. Furthermore, a nomogram was established and evaluated by C-index, calibration plot and ROC curve. Results The signature was established with the six genes ( ETF1, GSR, SKAP2, HSPD1, CACYBP and PNP ). Under the grouping from signature, patients in the high- risk group showed worse survival than those in the low-risk group in both three datasets. The univariate and multivariate Cox regression analysis indicated that mTORC1 related signature can be the potential independent prognostic factor in HCC. Conclusion The mTORC1 associated gene signature established and validated in our research could be used as a potential prognostic factor in HCC.

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USP10 suppresses tumor progression by inhibiting mTOR activation in hepatocellular carcinoma

Cited by 56 publications

References 31 publications

Decreased expression of ubiquitin-specific protease 10 correlates unfavorable prognosis in colorectal cancer

Decreased expression of ubiquitin-specific protease 10 correlates unfavorable prognosis in colorectal cancer

A Novel Signature Based On Mtorc1 Pathway In Hepatocellular Carcinoma

Idenfication of a novel signature based on mTORC1 pathway for hepatocellular carcinoma.

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