<i>USP4</i> expression independently predicts favorable survival in lung adenocarcinoma

Ming, Zhong; Jiang, Qi; Jin, Ronghui

doi:10.1002/iub.1755

Cited by 16 publications

(15 citation statements)

References 25 publications

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“…In line with these results, a protective effect of USP4 was reported in lung adenocarcinoma and breast cancer patients, although distinct effects of USP4 have been reported for other cancer types [48][49][50][51][52][53]. For instance, expression of USP4 was downregulated in lung adenocarcinoma, and low USP4 expression was associated with poor overall survival and recurrence-free survival [48]. Expression of USP4 was also significantly reduced in breast cancer tissue.…”

Section: Discussionsupporting

confidence: 63%

Epigenetic Silencing of Ubiquitin Specific Protease 4 by Snail1 Contributes to Macrophage-Dependent Inflammation and Therapeutic Resistance in Lung Cancer

Lai

Yeh

et al. 2020

Cancers

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There is a positive feedback loop driving tumorigenesis and tumor growth through coordinated regulation of epigenetics, inflammation, and stemness. Nevertheless, the molecular mechanism linking these processes is not well understood. In this study, we analyzed the correlation of de-ubiquitinases (DUBs) expression with survival data from the OncoLnc database. Among the DUBs analyzed, ubiquitin specific protease 4 (USP4) had the lowest negative Cox coefficient. Low expression of USP4 was associated with poor survival among lung cancer patients and was inversely correlated with expression of stemness and inflammation markers. Expression of USP4 were reduced at more advanced stages of lung cancer. Mechanistically, expression of USP4 was downregulated in snail1-overexpressing and stemness-enriched lung cancer cells. Snail1 was induced in lung cancer cells by interaction with macrophages, and epigenetically suppressed USP4 expression by promoter methylation. Stable knockdown of USP4 in lung cancer cells enhanced inflammatory responses, stemness properties, chemotherapy resistance, and the expression of molecules allowing escape from immunosurveillance. Further, mice injected with USP4 knockdown lung cancer cells demonstrated enhanced tumorigenesis and tumor growth. These results reveal that the Snail1-mediated suppression of USP4 is a potential mechanism to orchestrate epigenetic regulation, inflammation and stemness for macrophage-promoted tumor progression.

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Section: Discussionsupporting

confidence: 63%

Epigenetic Silencing of Ubiquitin Specific Protease 4 by Snail1 Contributes to Macrophage-Dependent Inflammation and Therapeutic Resistance in Lung Cancer

Lai

Yeh

et al. 2020

Cancers

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“…Previous studies have shown that USP4 expression was significantly decreased in breast cancer tissue and that USP4 inhibited breast cancer cell growth through inhibiting PDCD4 degradation 41 . USP4 was downregulated in lung adenocarcinoma and served as an independent predictor 42 . Some other studies claimed that USP4 might have oncogenic properties.…”

Section: Discussionmentioning

confidence: 97%

Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer

Liang

Song

et al. 2019

Molecular Therapy - Nucleic Acids

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Emerging evidence suggests that circular RNAs (circRNAs) have crucial roles in various processes, including cancer development and progression. However, the functional roles of circRNAs in breast cancer remain to be elucidated. In this study, we identified a novel circRNA (named circBMPR2) whose expression was lower in breast cancer tissues with metastasis. Moreover, circBMPR2 expression was negatively associated with the motility of breast cancer cells and significantly downregulated in human breast cancer tissues. Functionally, we found that circBMPR2 knockdown effectively enhanced cell proliferation, migration, and invasion. Moreover, circBMPR2 knockdown promoted tamoxifen resistance of breast cancer cells through inhibiting tamoxifen-induced apoptosis, whereas circBMPR2 overexpression led to decreased tamoxifen resistance. Mechanistically, we demonstrated that circBMPR2 could abundantly sponge miR-553 and that miR-553 overexpression could attenuate the inhibitory effects caused by circBMPR2 overexpression. We also found that ubiquitin-specific protease 4 (USP4) was a direct target of miR-553, which functions as a tumor suppressor in breast cancer. Our findings demonstrated that circBMPR2 might function as a miR-553 sponge and then relieve the suppression of USP4 to inhibit the progression and tamoxifen resistance of breast cancer. Targeting this newly identified circRNA may help us to develop potential novel therapies for breast cancer patients.

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“…Yao R et al suggested that esophageal cancer patients with high USP4 expression had relative longer survival time [43]. Some researchers also concluded that USP4 expression might be a favorable biomarker for OS and RFS in LUAD patients, while it was worth noting that USP4 expression has no prognostic value for OS and RFS in lung squamous cell carcinoma [44]. In addition, Ye et al suggested that USP4 had anti-cancer effect in breast cancer, and found that USP4 could inhibited the growth of tumors in a mouse tumor xenograft model [45].…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a 4-gene combination for the prognostication in lung adenocarcinoma patients

Yin

Zhao

et al. 2020

J. Cancer

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Objective: To identify a multi-gene prognostic factor in patients with lung adenocarcinoma (LUAD). Materials and methods Prognosis-related genes were screened in the TCGA-LUAD cohort. Then, patients in this cohort were randomly separated into training set and test set. Least absolute shrinkage and selection operator (LASSO) regression was performed to the penalized the Cox proportional hazards regression (CPH) model on the training set, and a prognostication combination based on the result of LASSO analysis was developed. By performing Kaplan-Meier curve analysis, univariate and multivariable CPH model on the overall survival (OS) as well as recurrence free survival (RFS), the prognostication performance of the multigene combination were evaluated. Moreover, we constructed a nomogram and performed decision curve analysis to evaluate the clinical application of the multigene combination. Results We obtained 99 prognosis-related genes and screened out a 4-gene combination (including CIDEC, ZFP3, DKK1, and USP4) according to the LASSO analysis. The results of survival analyses suggested that patients in the 4-gene combination low-risk group had better OS and RFS than those in the 4-gene combination high-risk group. The 4-gene mentioned was demonstrated to be independent prognostic factor of patients with LUAD in the training set(OS, HR=11.962, P<0.001; RFS, HR=9.281, P<0.001) and test set (OS, HR=5.377, P=0.003; RFS, HR=2.949, P=0.104). More importantly, its prognosis performance was well in the validation set (OS, HR=0.955, P=0.002; RFS, HR=1.042, P<0.001). Conclusions We introduced a 4-gene combination which could predict the survival of LUAD patients and might be an independent prognostic factor in LUAD.

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USP4 expression independently predicts favorable survival in lung adenocarcinoma

Cited by 16 publications

References 25 publications

Epigenetic Silencing of Ubiquitin Specific Protease 4 by Snail1 Contributes to Macrophage-Dependent Inflammation and Therapeutic Resistance in Lung Cancer

Epigenetic Silencing of Ubiquitin Specific Protease 4 by Snail1 Contributes to Macrophage-Dependent Inflammation and Therapeutic Resistance in Lung Cancer

Targeting the circBMPR2/miR-553/USP4 Axis as a Potent Therapeutic Approach for Breast Cancer

Development and validation of a 4-gene combination for the prognostication in lung adenocarcinoma patients

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