&lt;p&gt;Knockdown of USP8 Inhibits the Growth of Lung Cancer Cells&lt;/p&gt;

Rong, Zhenhua; Zhu, Zuoyan; Cai, Shihua; Zhang, Bingqing

doi:10.2147/cmar.s259191

Cited by 15 publications

(15 citation statements)

References 22 publications

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“…30 In addition, inhibition of USP8 reduced the expression of p-AKT and p-PI3K to suppress tumor cell proliferation and metastasis. 31,32 Activation of PI3K/AKT signaling inhibited Foxo1-mediated GSDMD expression, thus alleviating pyroptosis. 33 Our results showed that overexpression of USP8 attenuated lipopolysaccharide-induced decrease of PI3K and AKT phosphorylation in BEAS-2B, suggesting that USP8 promoted activation of PI3K/AKT signaling to suppress pyroptosis and airway inflammation in asthma.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-specific protease 8 inhibits lipopolysaccharide-triggered pyroptosis of human bronchial epithelial cells by regulating PI3K/AKT and NF-κB pathways

Liu

Huan

Wei

et al. 2022

aei

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Asthma, characterized by dysfunction of airway epithelial cells, is regarded as a chronic inflammatory disorder in the airway. Ubiquitin-specific protease 8 (USP8) belongs to ubiquitin proteasome system and mediates the stability of E3 ligases. The anti-inflammatory effect of USP8 has been widely investigated in distinct diseases, while the role of USP8 in asthma remains elusive. Firstly, human bronchial epithelial cells (BEAS-2B) were treated with lipopolysaccharide, which reduced the cell viability of BEAS-2B and induced the secretion of lactate dehydrogenase (LDH). Moreover, the expression of USP8 was downregulated in BEAS-2B post lipopolysaccharide treatment. Secondly, overexpression of USP8 enhanced cell viability of lipopolysaccharide-treated BEAS-2B, and reduced the LDH secretion. USP8 overexpression also attenuated lipopolysaccharide-induced upregulation of TNF-α, IL-6, and IL-1β in BEAS-2B. Thirdly, lipopolysaccharide treatment promoted the expression of NLRP3 (NLR Family Pyrin Domain Containing 3), N-terminal domain of gasdermin D (GSDMD-N), caspase-1, IL-1β, and IL-18 in BEAS-2B, which was inhibited by USP8 overexpression. Lastly, USP8 overexpression decreased the phosphorylation of NF-κB, while it increased the phosphorylation of PI3K and AKT in lipopolysaccharide-treated BEAS-2B. In conclusion, USP8 inhibited lipopolysaccharide-triggered inflammation and pyroptosis in human bronchial epithelial cells by activating PI3K/AKT signaling and inhibiting NF-κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Ubiquitin-specific protease 8 inhibits lipopolysaccharide-triggered pyroptosis of human bronchial epithelial cells by regulating PI3K/AKT and NF-κB pathways

Liu

Huan

Wei

et al. 2022

aei

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“…24 Silencing of USP8 inhibits the proliferation and migration of lung cancer cells. 25 Oncogenic function of USP8 is also observed in gastric cancer, cholangiocarcinoma, and breast cancer. [26][27][28] Apart from them, a growing body of evidence has demonstrated the tumor-promoting role of USP5 in different cancer types.…”

Section: Discussionmentioning

confidence: 99%

USP5 Promotes Uterine Corpus Endometrial Carcinoma Cell Growth and Migration via mTOR/4EBP1 Activation

Li¹,

Zhou²

2021

CMAR

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Background: Uterine corpus endometrial carcinoma (UCEC) is a common malignancy worldwide developed in the female reproductive system, which can be life-threatening due to metastasis and poor prognosis. Deubiquitinating enzymes (DUBs) play key roles in ubiquitin-proteasome system. As a member of DUBs, the ubiquitin-specific protease 5 (USP5) has been found to be an oncogene in several cancers. This study aims to explore the function of USP5 in UCEC. Materials and Methods: Clinical significance of USP5 was assessed from The Cancer Genome Atlas (TCGA) UCEC dataset. Knockdown and overexpression were performed by transfecting the cells with siRNAs and pCDNA3.1 vectors, respectively. CCK8, colony formation, wound healing, transwell, PI, and PI/annexin V staining were conducted to check the effect of USP5 on cellular biology function. Western blot assay was used to detect protein expression. Results: USP5 was upregulated in UCEC patients. Its downregulation led to decreased migration and proliferation of UCEC cells, and meanwhile, cell cycle arrest and apoptosis were induced. By contrast, USP5 overexpression significantly promoted cell migration and cell mitosis. Further study revealed that USP5 could cause hyperactivation of mTOR/4EBP1 pathway and rapamycin treatment could totally reverse the effects of UPS5 overexpression. Conclusion:Our data demonstrated that USP5 functioned as an oncogene in UCEC, which provided new insights into the pathogenesis of UCEC and a promising molecular target for UCEC diagnosis and therapy.

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“…Inhibition of USP8 has been shown to decrease NRDP1 levels and decrease cell proliferation and drug resistance in several cancers including breast, lung, and cervical cancer [47]. For example, knockdown of USP8 in lung cancer cells inhibited the proliferation of lung cancer cells by regulating several cell cycle and apoptosis-related proteins [48]. BRUCE (also known as BIRC6), an IAP, is a key regulator of USP8 activity.…”

Section: Discussionmentioning

confidence: 99%

Androgen Receptor-Mediated Nuclear Transport of NRDP1 in Prostate Cancer Cells Is Associated with Worse Patient Outcomes

Steele

Sam

Evans

et al. 2021

Cancers

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To our knowledge, our group is the first to demonstrate that NRDP1 is located in the nucleus as well as the cytoplasm of CaP cells. Subcellular fractionation, immunohistochemistry, and immunofluorescence analysis combined with confocal microscopy were used to validate this finding. Subcellular fractionation followed by western blot analysis revealed a strong association between AR and NRDP1 localization when AR expression and/or cellular localization was manipulated via treatment with R1881, AR-specific siRNA, or enzalutamide. Transfection of LNCaP with various NRDP1 and AR constructs followed by immunoprecipitation confirmed binding of NRDP1 to AR is possible and determined that binding requires the hinge region of AR. Co-transfection with NRDP1 constructs and HA-ubiquitin followed by subcellular fractionation confirmed that nuclear NRDP1 retains its ubiquitin ligase activity. We also show that increased nuclear NRDP1 is associated with PSA recurrence in CaP patients (n = 162, odds ratio; 1.238, p = 0.007) and that higher levels of nuclear NRDP1 are found in castration resistant cell lines (CWR22Rv1 and PC3) compared to androgen sensitive cell lines (LNCaP and MDA-PCa-3B). The combined data indicate that NRDP1 plays a role in mediating CaP progression and supports further investigation of both the mechanism by which nuclear transport occurs and the identification of specific nuclear targets.

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<p>Knockdown of USP8 Inhibits the Growth of Lung Cancer Cells</p>

Cited by 15 publications

References 22 publications

Ubiquitin-specific protease 8 inhibits lipopolysaccharide-triggered pyroptosis of human bronchial epithelial cells by regulating PI3K/AKT and NF-κB pathways

Ubiquitin-specific protease 8 inhibits lipopolysaccharide-triggered pyroptosis of human bronchial epithelial cells by regulating PI3K/AKT and NF-κB pathways

USP5 Promotes Uterine Corpus Endometrial Carcinoma Cell Growth and Migration via mTOR/4EBP1 Activation

Androgen Receptor-Mediated Nuclear Transport of NRDP1 in Prostate Cancer Cells Is Associated with Worse Patient Outcomes

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