Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer

Zhang, Yunkui; Wang, Tian; Zhang, Rongsheng; Zhang, Yujie; Ma, Hu

doi:10.1002/kjm2.12096

Cited by 21 publications

(22 citation statements)

References 30 publications

(57 reference statements)

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“…In the study of lung cancer, the decrease of USP44 expression level improves the invasive ability of tumor cells and reduces the overall survival rate of patients. The full name of TTC6 gene is Homo sapiens tetratricopeptide repeat domain 6 and its translation product TTC6 protein contains TPR structure and is a TPR protein (Allan & Ratajczak, 2011;Zhang et al, 2019). The important functions of TPR structure include transcriptional control, mitochondrial and peroxisome protein transport, protein kinase inhibition, NADPH oxidase activity, protein folding, immunity and virus replication (D'Andrea & Regan, 2003).…”

Section: Discussionmentioning

confidence: 99%

Diagnostic model of combined ceRNA and DNA methylation related genes in esophageal carcinoma

Guan

Yao

Bao

et al. 2020

PeerJ

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Esophageal cancer is a common malignant tumor in the world, and the aim of this study was to screen key genes related to the development of esophageal cancer using a variety of bioinformatics analysis tools and analyze their biological functions. The data of esophageal squamous cell carcinoma from the Gene Expression Omnibus (GEO) were selected as the research object, processed and analyzed to screen differentially expressed microRNAs (miRNAs) and differential methylation genes. The competing endogenous RNAs (ceRNAs) interaction network of differentially expressed genes was constructed by bioinformatics tools DAVID, String, and Cytoscape. Biofunctional enrichment analysis was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of the screened genes and the survival of the patients were verified. By analyzing GSE59973 and GSE114110, we found three down-regulated and nine up-regulated miRNAs. The gene expression matrix of GSE120356 was calculated by Pearson correlation coefficient, and the 11696 pairs of ceRNA relation were determined. In the ceRNA network, 643 lncRNAs and 147 mRNAs showed methylation difference. Functional enrichment analysis showed that these differentially expressed genes were mainly concentrated in the FoxO signaling pathway and were involved in the corresponding cascade of calcineurin. By analyzing the clinical data in The Cancer Genome Atlas (TCGA) database, it was found that four lncRNAs had an important impact on the survival and prognosis of esophageal carcinoma patients. QRT-PCR was also conducted to identify the expression of the key lncRNAs (RNF217-AS1, HCP5, ZFPM2-AS1 and HCG22) in ESCC samples. The selected key genes can provide theoretical guidance for further research on the molecular mechanism of esophageal carcinoma and the screening of molecular markers.

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Section: Discussionmentioning

confidence: 99%

Diagnostic model of combined ceRNA and DNA methylation related genes in esophageal carcinoma

Guan

Yao

Bao

et al. 2020

PeerJ

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“…And the ubiquitination process of proteins consists of at least five important components, including ubiquitin (Ub), ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), ubiquitin ligase (E3) and deubiquitinating enzyme (DUB). [1][2][3] At present, it is estimated that there are 1-2 E1s, 60-100 E2s, 1000 E3s and nearly 100 DUBs in human cells. 4 Among them, the disorder of protein ubiquitination components is closely related to the occurrence and development of cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>RING Finger Protein 38 Mediates LIM Domain Binding 1 Degradation and Regulates Cell Growth in Colorectal Cancer</p>

Huang

Yang

et al. 2020

OTT

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Background and Objectives: RING finger protein 38 (RNF38) has been reported to be involved in the tumorigenesis of several tumors, but its role in colorectal cancer (CRC) is still not investigated. In the present study, we aimed to investigate the effect of RNF38 in CRC cells. Materials and Methods: The public tumor databases GEPIA and Kaplan-Meier Plotter were used to analyze RNF38 expression and patients' overall survival in CRC. The qRT-PCR was carried out to assess the mRNA levels of RNF38 and LDB1. Western blot and co-immunoprecipitation were used to detect protein expression and ubiquitination. CCK-8 assay was performed to analyze CRC cell growth and viability. Results: RNF38 was found downregulated in CRC tumor tissues and cell lines, and CRC patients with high RNF38 expression had a longer overall survival than patients with low RNF38 expression. Our further investigations showed that RNF38 interacted with LDB1, and downregulated LDB1 expression by inducing its polyubiquitination. Moreover, overexpression of RNF38 inhibited CRC cell growth but enforced LDB1 could significantly antagonize RNF38-induced cell growth inhibition in CRC cells. Additionally, RNF38/LDB1 axis was involved in the drug sensitivity of 5-FU to CRC cells. Conclusion: Our studies suggested that RNF38 was functional in CRC cells, and downregulated CRC cell growth by inducing LDB1 polyubiquitination, which indicated that RNF38 could be as a novel target for CRC therapy.

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“…Therefore, the regulatory network of a USP on a tumor-cell signaling pathway is extremely complex. PI3K/AKT is a serine/threonine protein kinase involved in tumorigenesis (including ccRCC) [34]. If cells are stimulated by extracellular signals, PI3K activates AKT, and the latter further activates its downstream factor mTOR.…”

Section: Discussionmentioning

confidence: 99%

“…The downstream signaling pathway includes JNK, ERK and p38, which are associated with the growth and proliferation of tumor cells [36]. AKT-JNK/p38/ ERK has been shown to be involved in the progression of lung cancer and pancreatic cancer [34,37]. We measured the protein activity of JNK, AKT, ERK and p38.…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma

et al. 2020

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Background: Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. Ubiquitinspecific protease (USP)44 has been reported to be involved in various cancers. We investigated the function, role and molecular mechanism of USP44 in ccRCC. Methods: Data obtained from the Cancer Genome Atlas Data Portal and Gene Expression Omnibus database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. USP44 function in the proliferation and migration of tumor cells was assessed by cellular and molecular analyses using ccRCC lines (786-O cells and Caki-1 cells). Results: USP44 showed low expression in ccRCC cancer tissues compared with that in normal tissue. USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival. USP44 overexpression inhibited the proliferation and migration of 786-O cells and Caki-1 cells significantly. USP44 overexpression also prohibited cell proliferation by upregulating expression of P21, downregulating cyclin-D1 expression, and inhibiting cell migration by downregulating expression of matrix metalloproteinase (MMP)2 and MMP9. USP44 knockdown enhanced the proliferation and migration of 786-O cells and Caki-1 cells. USP44 function in inhibiting the proliferation and migration of 786-O cells and Caki-1 cells was associated with phosphorylation of Jun N-terminal kinase (JNK). Conclusion: USP44 may be a marker in predicting ccRCC progression. Inhibition by USP44 of the proliferation and migration of 786-O cells and Caki-1 cells is dependent upon the JNK pathway.

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Ubiquitin‐specific protease 44 inhibits cell growth by suppressing AKT signaling in non‐small cell lung cancer

Cited by 21 publications

References 30 publications

Diagnostic model of combined ceRNA and DNA methylation related genes in esophageal carcinoma

Diagnostic model of combined ceRNA and DNA methylation related genes in esophageal carcinoma

<p>RING Finger Protein 38 Mediates LIM Domain Binding 1 Degradation and Regulates Cell Growth in Colorectal Cancer</p>

Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma

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