Prognostic and predicted significance of Ubqln2 in patients with hepatocellular carcinoma

Luo, Yichen; Yu, Hongqiang; Liu, Xiaoyu; Deng, Hongkuan; Dai, Hai-Su; Fang, Lei; Zhang, Yujun; Lai, Jiansheng; Jiang, Yan; Shuai, Ling; Zhang, Lei-Da; Chen, Geng; Bie, Ping; Xie, Chuan‐Ming

doi:10.1002/cam4.3040

Cited by 3 publications

(4 citation statements)

References 28 publications

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“…In addition, efforts to identify new effective prognostic biomarkers for HCC are ongoing. According to previous reports, high expression levels of collagen type XXIV alpha 1 chain ( 43 ), ubiquilin 2 ( 44 ), sushi, von Willebrand factor type A, EGF and pentraxin domain containing 1 ( 45 ), acyl-CoA synthetase long chain family member 4 ( 46 ) and YTH N6-methyladenosine RNA binding protein 1 ( 47 ) are associated with the progression of HCC. Another study has demonstrated that in addition to the American Joint Committee on Cancer staging system, a long non-coding RNA-based risk score is another important factor affecting the overall survival of patients with HCC ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

et al. 2020

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Hepatocellular carcinoma (HCC) is a common malignant tumor in the clinic. Although there are increasing numbers of available treatment methods, their therapeutic effects are not satisfactory. The clinical indicators commonly used to predict the prognosis of HCC include tumor size, degree of cirrhosis, degree of tumor differentiation and tumor microvascular invasion; however, there are currently no molecular indicators that can predict the prognosis of HCC. Due to the differences in the progression of liver cancer among individuals, there is a growing need for prognostic biomarkers to accurately stratify patients for appropriate risk-adaptive treatment. The DNA topoisomerase 2-α (TOP2A) gene, which is located on human chromosome 17, encodes DNA topoisomerase IIα. Previous studies have demonstrated that TOP2A indicates a poor prognosis in patients with various types of tumors, but no such studies are currently available on HCC. By analyzing the differential expression of TOP2A in 50 pairs of tumor and paracancerous tissue samples in The Cancer Genome Atlas (TCGA) database, the present study revealed that the expression of TOP2A was significantly higher in tumor tissue compared with that in paracancerous tissue (P=6.319x10-16). In the collected clinical samples, the mRNA expression levels of TOP2A were significantly upregulated in HCC tumor tissues compared with those in the paracancerous tissues (P=6.40x10-3), suggesting that TOP2A was associated with the occurrence and development of liver cancer. In addition, the associations between TOP2A expression, clinicopathological features and prognosis were analyzed using a multi-center large sample dataset from TCGA database, and the results demonstrated that high expression of TOP2A was associated with a higher T stage, poorer clinical stage and higher histological grade compared with those in patients with low TOP2A expression. High expression of TOP2A was also identified to be associated with a poor prognosis of HCC, particularly in Asian populations. These results suggested that high expression of TOP2A in HCC tissues may be closely associated with tumor progression and metastasis, which may be used as a biological indicator to predict tumor prognosis in clinical practice.

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Section: Discussionmentioning

confidence: 99%

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

et al. 2020

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“…UBQLN2 had been identified as a risk factor for osteosarcoma [ 14 ] and a novel marker for detecting urothelial cancer cells [ 13 ]. Overexpression of UBQLN2 in hepatocellular carcinoma patients indicates a poor prognosis [ 10 ]. However, loss of UBQLN2 led to an epithelial-to-mesenchymal transition (EMT)-like change in lung adenocarcinoma cells and promoted the invasion and metastasis of lung cancer, as was also demonstrated [ 11 , 12 , 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is reported that UBQLN2 is associated with a variety of neurological diseases, including polyglutamine disease, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS) [8]. In addition to neurological diseases, UBQLN2 also plays an important role in malignant tumors [9][10][11][12][13][14][15]. In our previous work, we found that UBQLN2 had a potential role in the pathogenesis of ESCC [16].…”

Section: Introductionmentioning

confidence: 99%

Silencing UBQLN2 Enhances the Radiosensitivity of Esophageal Squamous Cell Carcinoma (ESCC) via Activating p38 MAPK

Wang

et al. 2023

Journal of Oncology

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Background. Ubiquilin 2 (UBQLN2) is an adaptor of ubiquitinated proteins and the proteasome. The potential role of UBQLN2 in carcinogenesis has been demonstrated. However, its role in modulating the radiosensitivity of cancer is not clear. Here, we explored the radiosensitizing effect of silencing UBQLN2 on esophageal squamous cell carcinoma (ESCC) and its mechanisms. Methods. We analyzed the prognostic role of UBQLN2 in the ESCC patient cohort from the Cancer Genomic Atlas (TCGA) database and our hospital. We also conducted a series of experiments in vivo and in vitro to investigate the effect of silencing UBQLN2 on ESCC radiosensitivity and its mechanisms. Results. UBQLN2 is highly expressed in ESCC tissues and positively correlated with poor overall survival (OS). The knockdown of UBQLN2 dramatically increased the radiosensitivity of ESCC cells. Mechanically, UBQLN2 suppression substantially upregulated p38 mitogen-activated protein kinases (MAPK). The p38 MAPK inhibitor SB203580 could reverse the radiation-enhancing effect induced by UBQLN2 knockdown. The direct interaction between UBQLN2 and p38 MAPK was confirmed by co-immunoprecipitation (CO-IP) assay. Furthermore, silencing UBQLN2 also inhibited the expression of phosphorylated DNA-dependent protein kinase catalytic subunit (p-DNA-PKcs) after irradiation. Finally, the xenografted tumor experiment confirmed the radiosensitizing effect of silencing UBQLN2 on ESCC in vivo. Conclusion. Our results suggest that silencing UBQLN2 enhances the radiosensitivity of ESCC by activating p38 MAPK, and UBQLN2 may be a potential target to enhance the radiosensitivity of ESCC.

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“…UBQLN1 expression positively correlates with patient overall outcome and survival rate in invasive breast carcinoma [27], gastric adenocarcinoma [24], and lung adenocarcinoma [26]. UBQLN2 shows similar prognostic potential in hepatocellular carcinoma (HCC) [160] and osteosarcoma [161]. However, UBQLN4 expression levels are increased in certain neuroblastomas and melanoma [38] and connected to worse outcomes.…”

Section: Ubqln Expression Levels Are Linked To Diseasementioning

confidence: 99%

Structure, dynamics and functions of UBQLNs: at the crossroads of protein quality control machinery

Zheng

Yang

Castañeda

2020

Biochemical Journal

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Cells rely on protein homeostasis to maintain proper biological functions. Dysregulation of protein homeostasis contributes to the pathogenesis of many neurodegenerative diseases and cancers. Ubiquilins (UBQLNs) are versatile proteins that engage with many components of protein quality control (PQC) machinery in cells. Disease-linked mutations of UBQLNs are most commonly associated with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other neurodegenerative disorders. UBQLNs play well-established roles in PQC processes, including facilitating degradation of substrates through the ubiquitin–proteasome system (UPS), autophagy, and endoplasmic-reticulum-associated protein degradation (ERAD) pathways. In addition, UBQLNs engage with chaperones to sequester, degrade, or assist repair of misfolded client proteins. Furthermore, UBQLNs regulate DNA damage repair mechanisms, interact with RNA-binding proteins (RBPs), and engage with cytoskeletal elements to regulate cell differentiation and development. Important to the myriad functions of UBQLNs are its multidomain architecture and ability to self-associate. UBQLNs are linked to numerous types of cellular puncta, including stress-induced biomolecular condensates, autophagosomes, aggresomes, and aggregates. In this review, we focus on deciphering how UBQLNs function on a molecular level. We examine the properties of oligomerization-driven interactions among the structured and intrinsically disordered segments of UBQLNs. These interactions, together with the knowledge from studies of disease-linked mutations, provide significant insights to UBQLN structure, dynamics and function.

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Prognostic and predicted significance of Ubqln2 in patients with hepatocellular carcinoma

Cited by 3 publications

References 28 publications

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

High expression of TOP2A in hepatocellular carcinoma is associated with disease progression and poor prognosis

Silencing UBQLN2 Enhances the Radiosensitivity of Esophageal Squamous Cell Carcinoma (ESCC) via Activating p38 MAPK

Structure, dynamics and functions of UBQLNs: at the crossroads of protein quality control machinery

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