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Protein and mRNA level of USP39 in CRC patients. (A) mRNA level of USP39 in tumor tissues and corresponding adjacent normal tissues, using GAPDH as a loading control. (B) Protein level of USP39 in tumor tissues and corresponding adjacent normal tissues, using GAPDH as a loading control. (TT, tumor tissues; AT, adjacent normal tissues).
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In the present study, we first examined the expression of USP39 protein using tissue array containing 90 colorectal cancer (CRC) tissues and 9 clinical samples, and observed that it has significantly higher expression in cancer tissues as compared to the corresponding adjacent normal tissues. Also, we tested USP39 expression level in four CRC cance...
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... with poor patient overall survival. The USP39 expression was examined in human CRC tissue array samples by immunohistochemical staining. The array included 90 CRC patient tissue samples including cancer and corre- sponding adjacent normal tissues. Among these, 48 tissues samples were from male patients, while 42 were from female patients, with a median age of 71 years (range, 24-90 years). As shown in Table Ⅰ and Fig. 1A, USP39 had strong expres- sion in CRC tumor tissue samples, as 89 of these showed a score of ≥2. In contrast, adjacent normal tissue samples displayed dramatically reduced USP39 expression, compared with cancer tissues (P<0.001). In addition, USP39 expression was not associated with other factors. However, Kaplan- Meier survival curves and the log-rank test survival analysis indicated that CRC patients with high USP39 expression had significantly poor overall survival (P<0.05), as shown in Fig. 1B. Additionally, the tissue sample analysis of 9 colorectal patients, also revealed significantly higher mRNA and protein levels of USP39 in tumor tissues than corresponding adjacent normal tissues, as shown in Fig. 2. cell lines, loVo, Caco2, SW480 and HT-29, using western blot analysis, as shown in Fig. 3A. Our results indicated that indeed all these cell lines have elevated expression of USP39. Next, we knocked down the USP39 expression in these CRC cells and analyzed its effects on their growth, using MTT ...
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Background/aims:
In recent years the diagnosis and management of renal cancer has changed greatly, although the mechanism is still elusive. TMEM106a is a conserved type II transmembrane protein which is a key factor to regulate macrophage activation. Its inactivation in gastric cancer is frequently observed to be associated with poor prognosis. Th...
Citations
... Research has proved that USP5 promoted the growth and chemoresistance of colorectal cancer cells, which relied on its deubiquitylation on several oncogenes [13]. Evidence suggests that the USP39 protein contributes to not only the growth but also the metastasis of colorectal cancer [14]. As the emerging oncogenic role of USPs in multiple cancers, agents targeting USP has become a promising therapeutic strategy for patients with cancer. ...
Ubiquitin-specific protease 36 (USP36) has been reported to exhibit oncogenic effects in various malignancies, but the function of USP36 in colon cancer progression remains indefinite. Herein, we aimed to determine the role and mechanism of USP36 in malignant phenotypes of colon cancer cells and explore the potential drug targeting USP36. Bioinformatics analyses indicated that USP36 is highly expressed and significantly related to tumor stages in colon cancer. Besides, USP36 was further up-regulated in oxaliplatin (Oxa)-resistant colon cancer cells. Colony formation, Edu staining, Transwell, wound healing, sphere formation, and CCK-8 assays were conducted and showed that the proliferation, Oxa-resistance, migration, stemness, and invasion of HCT116 cells were promoted after overexpressing USP36, while suppressed by USP36 knockdown. Mechanically, USP36 enhances c-Myc protein stabilization in HCT116 cells via deubiquitination. AutoDock tool and ubiquitin-AMC hydrolysis assay identified cinobufotalin (CBF), an anti-tumor drug, maybe a USP36 inhibitor by inhibiting its deubiquitination activity. CBF significantly prohibited proliferation, migration, invasion, and stemness of HCT116 cells and reversed Oxa-resistance, whereas enforced expression of USP36 blocked these effects. Moreover, in vivo analyses confirmed the oncogenic role of USP36 and the therapeutic potential of CBF in the malignancy of colon cancer. In conclusion, CBF may be a promising therapeutic agent for colon cancer due to its regulation of the USP36/c-Myc axis.
... USP18 is negatively associated with cell apoptosis in breast cancer [30]. USP39 knockdown induces cell apoptosis via the regulation the Wnt/β-catenin signaling pathway in colorectal cancer [31]. It has been shown that the mechanism underlying cisplatin resistance is related to apoptosis [32][33][34]. ...
... The Wnt/β-catenin signaling pathway is an important cellular signaling pathway in cancer and is profoundly influenced by the activity of USPs [49]. Previous studies have reported that USP39 silencing inhibits colon cancer cell growth and metastasis, and induces apoptosis by regulating the Wnt/β-catenin signaling pathway [31]. β-catenin, acting as an intracellular signal transducer in the Wnt/β-catenin signaling pathway, plays a key role in tumorigenesis [21]. ...
Epithelial ovarian cancer (EOC) is the leading cause of cancer death all over the world. USP43 functions as a tumor promoter in various malignant cancers. Nevertheless, the biological roles and mechanisms of USP43 in EOC remain unknown. In this study, USP43 was highly expressed in EOC tissues and cells, and high expression of USP43 were associated with a poor prognosis of EOC. USP43 overexpression promoted EOC cell proliferation, enhanced the ability of migration and invasion, decreased cisplatin sensitivity and inhibited apoptosis. Knockdown of USP43 in vitro effectively retarded above malignant progression of EOC. In vivo xenograft tumors, silencing USP43 slowed tumor growth and enhanced cisplatin sensitivity. Mechanistically, USP43 inhibited HDAC2 degradation and enhanced HDAC2 protein stability through its deubiquitylation function. USP43 diminished the sensitivity of EOC cells to cisplatin through activation of the Wnt/β-catenin signaling pathway mediated by HDAC2. Taken together, the data in this study revealed the functions of USP43 in proliferation, migration, invasion, chemoresistance of EOC cells, and the mechanism of HDAC2-mediated Wnt/β-catenin signaling pathway. Thus, USP43 might serve as a potential target for the control of ovarian cancer progression.
... Previous studies have shown that USP39 has the potential to determine the prognosis of patients with solid cancer (Yuan et al., 2017). Liao et al., (2021) showed that the expression of USP39 was increased in hepatocellular carcinoma (HCC) tissue compared to non-tumor tissue and showed a poorer prognosis. ...
... For the last few years, several studies regarding the role of USP39 as a prognosis predictor in several cancers have been conducted, but variable results have been reported. USP39 is a deubiquitinating enzyme essential for pre-mRNA splicing but does not have protease activity (Yuan et al., 2017). USP39 is a member of the deubiquitylation family. ...
Objectives:
This meta-analysis aimed to evaluate the association between USP39 expression, the prognosis of patients with solid cancer, and to identify the clinicopathological characteristics of these patients.
Material and method:
This study was carried out using PRISMA strategy. Pubmed, ScienceDirect, Google Scholar, Ebsco, Cochrane Library electronic databases were searched for relevant studies published up to April 2022. 14 studies was included in this study. Hazard ratio (HR) and 95% confidence interval (CI) data were collected, including number of samples, detection methods, number of sample with high USP39 expression, and cut-off value. HR and 95% CI was used to evaluate the prognostic value of USP39 expression. Odds ratio (OR) with 95% CI was used to assess the effect of USP39 expression on clinicopathological parameters.
Results:
Qualitative analysis using 14 included studies and quantitative analysis using 7 included studies. We found that USP39 expression has significant risk for histological grade (OR 3.14, CI 95% 2.15-4.58, p<0.001), TNM stage (OR 2.23, CI 95% 1.66-3.00, p<0.001), tumor size (OR 2.17, CI 95% 1.56-3.03, p<0.001), lymph node metastasis (OR 2.31, CI 95% 1.23-4.33, p=0.009), vascular invasion (OR = 1.76, 95% CI = 1.13-2.73, p=0.01). Furthermore, high expression of USP39 protein was associated with worse OS (OR 1.17, CI 95% 1.13-1.21, p<0.001) and DFS (OR 1.39, CI 95% 1.23-1.57, p<0.001) in cancer patients.
Conclusion:
It can be concluded that USP39 has a significant prognostic value in patients with solid cancer and was found to have a significant relationship in the clinicopathology of solid cancer patients.
... USP39 was observed to maintain the stability of oncogenes through deubiquitination enzyme activity [8,57,58,72,73]. In addition, USP39 is also known to promote tumor progression by regulating oncogenes or tumor suppressor genes [3,6,12,74]. In this study, we discovered a new mechanism involving USP39 that leads to the inhibition of ubiquitination by competitive APC/ Cdh1 binding to FOXM1 (Figures 2D and 8). ...
Deubiquitinating enzyme dysregulation has been linked to the development of a variety of human malignancies, including breast cancer. However, the exact involvement of the deubiquitinating enzyme USP39 in the progression of breast cancer is yet unknown. Cell viability and colony formation analysis was used to assess the effects of USP39 knockdown on breast cancer cells in this study. The interaction between USP39 and FOXM1 was investigated using co-immunoprecipitation (co-IP) and in vitro deubiquitination analysis. The expression of USP39 and FOXM1 in breast cancer tissues was studied using the TCGA database. According to our findings, USP39 deubiquitinates and stabilizes FOXM1, promoting breast cancer cell proliferation, colony formation, and tumor growth in vivo. Furthermore, elevated USP39 expression lowers FOXM1 ubiquitination, resulting in increased transcriptional activity. In addition, the high expression of USP39 reduces the ubiquitination of FOXM1, thereby enhancing the transcriptional activity of FOXM1 and regulating the expression of downstream genes Cdc25b and Plk1. USP39 is positively correlated with the expression level of FOXM1 in breast cancer cells. In general, our research revealed the USP39-FOXM1 axis as a critical driver of breast cancer cell proliferation and provided a theoretical foundation for targeting the USP39-FOXM1 axis for pancreatic cancer treatment.
... Studies have shown that USP39 knockout inhibits the migration and invasion of colon cancer cells. In addition, the expression of key proteins in the Wnt/β-catenin pathway is reduced, further affecting the growth and metastasis of CRC [125]. The USP7 inhibitor P5090 reduces the activity of Wnt signaling by enhancing ubiquitination and degradation of β-catenin, indicating its role in cancer progression [126]. ...
Deubiquitinases (DUBs) deconjugate ubiquitin (UBQ) from ubiquitylated substrates to regulate its activity and stability. They are involved in several cellular functions. In addition to the general biological regulation of normal cells, studies have demonstrated their critical roles in various cancers. In this review, we evaluated and grouped the biological roles of DUBs, including proliferation, metastasis, and apoptosis, in the most common cancers in the world (liver, breast, prostate, colorectal, pancreatic, and lung cancers). The current findings in these cancers are summarized, and the relevant mechanisms and relationship between DUBs and cancers are discussed. In addition to highlighting the importance of DUBs in cancer biology, this study also provides updated information on the roles of DUBs in different types of cancers.
... Increases expression of b-catenin, TCF4, MMP2 and MMP9Cell growth, migration, and invasion[72] USP20 Ubiquitin-specific peptidase 20 (DUB) Regulates b-catenin stability by deubiquitination Proliferation, invasion and migration[73] Phosphorylates b-catenin at Ser552 and Ser675DDB2 Damage-specific DNA-binding protein 2 Restricts Wnt signaling by removing Wnt receptors from cell surface and activating RNF43 DHX32 DEAH-box helicase 32 (Putative) Suppresses expression of WISP1, MMP7, and VEGFA in the Wnt pathway Proliferation, migration and invasion [78] Twa1/ Gid8 Two hybrid-associated protein no.1 with RanBPM Facilitates b-catenin nuclear retention Promotes b-catenin translocation into nucleus via FZD6 interaction Cell proliferation and liver metastasis [80] EDAR Ectodysplasin A receptor Activates b-catenin/c-Myc signaling pathway ...
The Wnt/β-catenin signaling pathway has been implicated as the central mechanism that drives colorectal carcinogenesis. Its activation is historically due to mutation on APC (adenomatous polyposis coli), resulting to nuclear localization of β-catenin and expression of Wnt target genes that promote tumor progression. Although this pathway seems to be a pivotal therapeutic target because of its critical role in colorectal cancer, there has been no clinically approved therapies targeting Wnt/β-catenin signaling pathway to this date. Here, we reviewed the recent progress of this signal transduction pathway in colorectal tumorigenesis. Apart from their roles in cancer initiation, the new pathway modulators (activators and repressors) also participate in chemoresistance, epithelial-mesenchymal transition and cancer stem cell renewal. Of the proteins reported to modulate this pathway, CDX2 (Caudal-related homeobox transcription factor 2) showed potentials as promising molecular target. CDX2 warrants further studies to determine its significance as molecular target for colorectal cancer therapeutics. Overall, the regulation of Wnt/β-catenin signaling pathway remains intriguingly complex and is not fully understood in spite of the widespread research efforts. Its intricacy remains a major barrier in the development of chemotherapeutic agent that specifically targets it.
... Furthermore, the Wnt/βcatenin signaling is associated with CRC development [27]. The former reports have indicated this signaling pathway contributed to CRC growth, metastasis and chemoresistance to 5-FU and oxaliplatin [28][29][30]. Hence, we further explored and found circPTK2 knockdown blocked the Wnt/β-catenin pathway. ...
Statement of Retraction
We, the Editors and Publisher of the journal Bioengineered, have retracted the following article:
Zhipeng Jiang, Zehui Hou, Wei Liu, Zhuomin Yu, Zhiqiang Liang & Shuang Chen (2022) Circular RNA protein tyrosine kinase 2 (circPTK2) promotes colorectal cancer proliferation, migration, invasion and chemoresistance, Bioengineered, 13:1, 810-823, DOI: 10.1080/21655979.2021.2012952
Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to satisfactorily address the concerns raised and have not been able to provide their original data in the appropriate format. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. The authors do not agree with the retraction.
We have been informed in our decision-making by our editorial policies and the COPE guidelines.
The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.
... Many molecular signaling pathways are involved in CRC initiation and progression, such as ERK/MAPK, TGF-β, PI3K/Akt, Src/FAK, and β-catenin pathways. These pathways can promote the hallmarks of cancer such as inflammation, angiogenesis, metastasis, and invasion, also via the activation and overexpression of MMPs [6,7]. Thus, MMPs have been suggested as potential prognostic factors for the malignancy risk of colorectal polyps. ...
Colorectal cancer (CRC) is the third and second cancer for incidence and mortality worldwide, respectively, and is becoming prevalent in developing countries. Most CRCs derive from polyps, especially adenomatous polyps, which can gradually transform into CRC. The family of Matrix Metalloproteinases (MMPs) plays a critical role in the initiation and progression of CRC. Prominent MMPs, including MMP-1, MMP-2, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, MMP-14, and MMP-21, have been detected in CRC patients, and the expression of most of them correlates with a poor prognosis. Moreover, many studies have explored the inhibition of MMPs and targeted therapy for CRC, but there is not enough information about the role of MMPs in polyp malignancy. In this review, we discuss the role of MMPs in colorectal cancer and its pathogenesis.
... Many molecular signaling pathways are involved in CRC initiation and progression, such as ERK/MAPK, TGF-β, PI3K/Akt, Src/FAK, and β-catenin pathways. These pathways can promote the hallmarks of cancer such as inflammation, angiogenesis, metastasis, and invasion, also via the activation and overexpression of MMPs [6,7]. Thus, MMPs have been suggested as potential prognostic factors for the malignancy risk of colorectal polyps. ...
Colorectal cancer (CRC) is the third and second cancer for incidence and mortality worldwide, respectively, and is becoming prevalent in developing countries. Most CRCs derive from polyps, especially adenomatous polyps, which can gradually transform into CRC. The family of Matrix Metalloproteinases (MMPs) plays a critical role in the initiation and progression of CRC. Prominent MMPs, including MMP-1, MMP-2, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, MMP-14, and MMP-21, have been detected in CRC patients, and the expression of most of them correlates with a poor prognosis. Moreover, many studies have explored the inhibition of MMPs and targeted therapy for CRC, but there is not enough information about the role of MMPs in polyp malignancy. In this review, we discuss the role of MMPs in colorectal cancer and its pathogenesis
... Snail, a direct target of the β-catenin/TcF complex and also an EMT-initiating gene, is upregulated in the process of EMT (59) and is known to activate EMT during cancer metastasis (12). Recently, certain results suggested that β-catenin-mediated expression of MMPs also induces EMT and increases the migratory and invasive capabilities of cRc cells via MMP-mediated degradation of the extracellular matrix (1,60). ...
... Additionally, negative regulatory targets inhibit cRc progression via inactivating Wnt/β-catenin signaling, and these targets include tumor suppressor genes (167,168), metastasis-suppressor genes (169), ubiquitin-like proteins (170) and anticancer bioactive peptides (171). In the present review, the effects of these therapy targets on cRc in the Wnt/β-catenin signaling pathway are presented in Table II (3,4,21,35,52,60,105,(160)(161)(162)(163)(164)(165)(166)(167)(168)(169)(170)(171)(172)(173)(174)(175)(176)(177)(178). ...
Colorectal cancer (CRC) is one of the most common carcinomas. Although great progress has been made in recent years, CRC survival remains unsatisfactory due to high metastasis and recurrence. Understanding the underlying molecular mechanisms of CRC tumorigenesis and metastasis has become increasingly important. Recently, aberrant Wnt/β‑catenin signaling has been reported to be strongly associated with CRC tumorigenesis, metastasis and recurrence. Therefore, the Wnt/β‑catenin signaling pathway has potential value as a therapeutic target for CRC. In the present review, the dysregulation of this pathway in CRC and the promoting or suppressing function of therapeutic targets on CRC were explored. In addition, the interaction between this pathway and epithelial‑mesenchymal transition (EMT), cell stemness, mutations, metastasis‑related genes and tumor angiogenesis in CRC cells were also investigated. Numerous studies on this pathway may help identify the potential diagnostic and prognostic markers and therapeutic targets for CRC.
