Prognostic significance of Ubiquilin1 expression in invasive breast cancer

Wang, Yunchao; Lu, Janice; Zhao, Xia; Feng, Yu; Lv, Shuzhen; Mu, Ying; Wang, Dandan; Fu, Hui; Chen, Yizhi; Li, Yanping

doi:10.3233/cbm-150503

Cited by 16 publications

(20 citation statements)

References 20 publications

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“…The family of adapter proteins, Ubiquilins (UBQLNs), are lost in multiple types of cancers as well as in AD (Beverly, Lockwood, Shah, Erdjument-Bromage, & Varmus, 2012; Viswanathan et al, 2011; Y. Wang et al, 2015). This family consists of five members; UBQLN1-4 and UBQLNL, which contains an N-terminus ubiquitin-like (UBL) domain and a C-terminus ubiquitin-associated (UBA) domain (Kleijnen et al, 2000; Z.…”

Section: Introductionmentioning

confidence: 99%

Ubiquilin proteins regulate EGFR levels and activity in lung adenocarcinoma cells

Kurlawala

Saurabh

Dunaway

et al. 2020

Preprint

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19Ubiquilin proteins (UBQLNs) are involved in diverse cellular processes like ERAD 20 (endoplasmic reticulum associated degradation), autophagy, apoptosis and epithelial to 21 mesenchymal transition. UBQLNs interact with a variety of substrates, including cell 22 surface receptors, transcription factor regulators, proteasomal machinery proteins, and 23 transmembrane proteins. Additionally, previous work from our lab shows that UBQLN1 24 interacts with IGFR family members (IGF1R, IGF2R, INSR) and this interaction regulates 25 the activity and proteostasis of IGFR family members. Here, we examined regulation of 26 UBQLN1 with Epidermal Growth Factor Receptor (EGFR) in lung adenocarcinoma cells. 27 2 Loss of UBQLN1 occurs at high frequency in human lung cancer patient samples and we 28 have shown that loss of UBQLN1 is capable altering processes involved in cell 29 proliferation, migration, invasion and epithelial to mesenchymal transition in lung 30 adenocarcinoma cell lines. Here, we present data that loss of UBQLN1 resulted in 31 increased turnover of total EGFR, whilst increasing the relative amount of active EGFR 32 in lung adenocarcinoma cells, especially in the presence of its ligand EGF. Furthermore, 33 loss of UBQLN1 led to a more invasive cell phenotype as manifested by increased 34 proliferation, migration and speed of movement of these lung adenocarcinoma cells. 35Taken together, UBQLN1 regulates expression and stability of IGFRs and EGFR, 36 members of the receptor tyrosine kinase family of proteins in lung cancer cells. 37

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Section: Introductionmentioning

confidence: 99%

Ubiquilin proteins regulate EGFR levels and activity in lung adenocarcinoma cells

Kurlawala

Saurabh

Dunaway

et al. 2020

Preprint

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“…Also, many studies have revealed the vital role of UBQLNs in the progression of various human cancers. Ubiquilin -2 is involved in migration and invasion of breast cancer [10] and lung cancer cells [11]. A recent study showed that UBQLN4 could curtail HRR activity by removing MRE11 from damaged chromatin and provide a therapeutic target for PARP1 inhibitor treatment in UBQLN4-overexpressing tumors [12].…”

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confidence: 99%

UBQLN4 promotes progression of HCC via activating wnt-β-catenin pathway and is regulated by miR-370

Cui

et al. 2020

Cancer Cell Int

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Background: Ubiquilin-4 (UBQLN4) is a member of the ubiquitin-proteasome system that is usually upregulated in many tumor cells. Its overexpression has been associated with poor disease outcomes in various cancer diseases. However, the underlying mechanism of UBQLN4 in the development of hepatocellular carcinoma (HCC) has not been elucidated.Methods: Immunochemistry, real-time PCR, and western blotting were used to evaluate the expression levels of UBQLN4 in cancer tissues. Univariate, Cox-regression, and Kaplan-Meier analyses were performed to determine the association between UBQLN4 expression and HCC prognosis. Cell Counting Kit-8 (CCK-8), transwell, EDU and colony formation assays were conducted to evaluate the role of UBQLN4 in HCC cell progression. The gene set enrichment analysis and luciferase reporter experiments were conducted to find the mechanism of UBQLN4 in HCC.Results: Ubiquilin-4 (UBQLN4) was overexpressed in HCC tissues. Besides, overexpression of UBQLN4 was associated with poor overall survival and disease-free survival rate of HCC patients. The loss-of-function analysis revealed that suppression of UBQLN4 inhibited the proliferation and invasion of HCC cells in vivo and in vitro. The KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that UBQLN4 could regulate activation of the wnt-β-catenin pathway in HCC cells. Furthermore, our results showed that UBQLN4 was downregulated by miR-370, which acted as a tumor suppressor gene in HCC progression. Conclusion:The results of the present study suggest that the miR-370/UBQLN4 axis may play a critical role in the progression of HCC. These findings may inform future strategies for the development of therapeutic agents against HCC. BackgroundHepatocellular carcinoma (HCC) is one of the most common and highly malignant solid tumors, and is the thirdleading cause of cancer-related deaths worldwide [1,2].Many treatment options for HCC exist, including surgical resection, liver transplantation (LT), transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA) and molecular targeted therapy (sorafenib). These treatments can greatly improve the 5-year survival rate of HCC [3,4]. However, because of the heterogeneity and high invasiveness of HCC cells, recurrence and metastasis are still common. Therefore, finding molecular markers for recurrence and metastasis in HCC is necessary for the improvement of survival rates of patients.

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“…A previous study reported that overexpression of LAMB1 is associated with both poor OS and DFS in breast cancer [14]. In addition, Yunchao et al reported that Ubiquitin1, encoded by UBQLN1, is associated with poor prognosis in breast cancer [36]. As this gene interacts with ubiquitin conjugating enzyme E2 variant 1 (encoded by UBE2V1, which was detected as a gene associated with OS, Table 2), this UBE2V1 seems to be a novel molecular biomarker able to predict poor prognosis in breast cancer.…”

Section: Discussionmentioning

confidence: 97%

The prediction models for postoperative overall survival and disease‐free survival in patients with breast cancer

et al. 2017

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The goal of this study is to establish a method for predicting overall survival (OS) and disease‐free survival (DFS) in breast cancer patients after surgical operation. The gene expression profiles of cancer tissues from the patients, who underwent complete surgical resection of breast cancer and were subsequently monitored for postoperative survival, were analyzed using cDNA microarrays. We detected seven and three probes/genes associated with the postoperative OS and DFS, respectively, from our discovery cohort data. By incorporating these genes associated with the postoperative survival into MammaPrint genes, often used to predict prognosis of patients with early‐stage breast cancer, we constructed postoperative OS and DFS prediction models from the discovery cohort data using a Cox proportional hazard model. The predictive ability of the models was evaluated in another independent cohort using Kaplan–Meier (KM) curves and the area under the receiver operating characteristic curve (AUC). The KM curves showed a statistically significant difference between the predicted high‐ and low‐risk groups in both OS (log‐rank trend test P = 0.0033) and DFS (log‐rank trend test P = 0.00030). The models also achieved high AUC scores of 0.71 in OS and of 0.60 in DFS. Furthermore, our models had improved KM curves when compared to the models using MammaPrint genes (OS: P = 0.0058, DFS: P = 0.00054). Similar results were observed when our model was tested in publicly available datasets. These observations indicate that there is still room for improvement in the current methods of predicting postoperative OS and DFS in breast cancer.

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Prognostic significance of Ubiquilin1 expression in invasive breast cancer

Abstract: The expression level of UBQLN1 and prognosis in breast cancer is clarified for the first time and UBQLN1 seems to be a novel molecular marker to predict poor prognosis in breast cancer.

Cited by 16 publications

References 20 publications

Ubiquilin proteins regulate EGFR levels and activity in lung adenocarcinoma cells

Ubiquilin proteins regulate EGFR levels and activity in lung adenocarcinoma cells

UBQLN4 promotes progression of HCC via activating wnt-β-catenin pathway and is regulated by miR-370

The prediction models for postoperative overall survival and disease‐free survival in patients with breast cancer

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