OTUB1 promotes metastasis and serves as a marker of poor prognosis in colorectal cancer

Zhou, Yi; Wu, Jiangxue; Fu, Xiang; Du, Wei; Zhou, Ling; Meng, Xiangqi; Yu, Hongyan; Lin, Jiaxin; Ye, Wen; Liu, Jiani; Peng, Hui; Liu, Ran Yi; Pan, Ci; Huang, Wenlin

doi:10.1186/1476-4598-13-258

Cited by 77 publications

(79 citation statements)

References 49 publications

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“…Previous studies have shown that OTUB1 could activate the TGF‐β signaling pathway by inhibiting the ubiquitin of active Smad2/3 . TGF‐β signaling pathway is believed to exert a crucial function in the progression of EMT, and there already have been reports confirming that OTUB1 could promote the migration of colorectal cancer and gastric adenocarcinoma by inducing EMT . In this study, we found down‐regulation of OTUB1 could inhibit the migration capacity of glioma cells through wound‐healing assay and transwell assay.…”

Section: Discussionsupporting

confidence: 53%

“…Nevertheless, the expression and function of P53 gene were often lost in the occurrence and development of tumors . Recent research indicated that OTUB1 might be associated with the invasion and migration of a variety of malignant tumors (such as gastric adenocarcinoma, colorectal cancer and breast cancer) and predicted poor prognosis . We hypothesized that OTUB1 probably has complex functions in different types of malignant tumors, due to the reason that it participates in a variety of cell signal‐transduction pathways, as well as regulating the expression and activity of different substrates .…”

Section: Discussionmentioning

confidence: 99%

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Silencing of OTUB1 inhibits migration of human glioma cells in vitro

Bao

et al. 2017

Neuropathology

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OTU domain-containing ubiquitin aldehyde-binding protein 1 (OTUB1) protein, a deubiquitinating enzyme (DUB) which belongs to the ovarian tumor (OTU) family, was reported to be associated with the development of various malignancies. However, the potential function of OTUB1 in human gliomas was still unclear. In this study, we sought to investigate the function of OTUB1 in the pathological process of gliomas and analyze its related clinical significance. Western blot and immunohistochemistry analyses demonstrated that OTUB1 was overexpressed in glioma tissues, and statistical analysis suggested the expression level of OTUB1 was significantly correlated with the WHO grades of human gliomas (P < 0.05). Moreover, Kaplan-Meier curve also indicated that high expression of OTUB1 was correlated with a poor prognosis. In vitro, silencing OTUB1 retarded the migration ability of glioma cells. Knockdown of OTUB1 increases epithelial-mesenchymal transition-related protein E-cadherin expression, but decreases simultaneously the expression of vimentin and snail. Furthermore, down-regulated expression of OTUB1 also resulted in decreased expression of some extracellular matrix degradation-related proteins, such as matrix metallopeptidase (MMP)2 and MMP9. All results suggested that OTUB1 was a valuable marker in the pathogenesis of human gliomas and could be used as a novel biomarker for glioma therapy in the future.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Silencing of OTUB1 inhibits migration of human glioma cells in vitro

Bao

et al. 2017

Neuropathology

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“…OTUB1 is abnormally up‐regulated in somatic malignancies and exerts oncogenic functions 26, 32, 33, 34. We have also previously demonstrated that OTUB1 prompted tumour growth and metastasis in ovarian cancer and gastric carcinoma 25, 29.…”

Section: Discussionmentioning

confidence: 80%

The non‐coding RNA OTUB1‐isoform2 promotes ovarian tumour progression and predicts poor prognosis

Wang

Ning

Wei

et al. 2018

J Cellular Molecular Medi

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Ovarian cancer is the leading malignancy of the female reproductive system and is associated with inconspicuous early invasion and metastasis. We have previously reported that the oncogene OTUB1 plays a crucial role in ovarian cancer progression, but the role of its isoform, the non‐coding RNA OTUB1‐isoform2, in ovarian cancer is still elusive. Here, we reported that OTUB1‐isoform2 expression in ovarian cancer tissues was significantly higher than that in the paired paratumorous tissues (P < .01). The patients with high expression of OTUB1‐isoform2 had larger tumours than those with low expression (P < .05). The high expression of OTUB1‐isoform2 was correlated with the involvement of bilateral ovaries (P < .05), lymph node metastasis (P < .05), vascular invasion (P < .05), greater omentum involvement (P < .01), fallopian tube involvement (P < .05), advanced FIGO stages (P < .01) and recurrence (P < .01). Moreover, OTUB1‐isoform2 served as an independent negative prognostic predictor for disease‐free survival (DFS) and disease‐specific survival (DSS). Overexpression of OTUB1‐isoform2 in the ovarian cancer cells stimulated cell proliferation, migration and invasion both in vitro and in vivo. In summary, our study suggested that OTUB1‐isoform2 is a novel prognostic biomarker with independent oncogenic functions for ovarian cancer.

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“…Protein levels of ASB3 were detected by immunohistochemical (IHC) assay with a peroxidase kit (DAKO, Carpinteria, CA, USA) as described previously [26, 27]. Briefly, after routine deparaffinization, rehydration, and blocking with 0.3% H 2 O 2 and antigen retrieval, the slides were incubated overnight at 4 °C with rabbit anti-ASB3 antibody (1:400, NBP1-88,812; Novus Biologicals), followed by incubation with HRP-conjugated secondary antibody and visualized with the EnVision Detection Kit (DAKO).…”

Section: Methodsmentioning

confidence: 99%

“…One million HCT116 cells overexpressing WT ASB3 or ASB3 mutants or control cells in 20 μL PBS were respectively injected into the distal tip of the spleen (8 mice per group). Six weeks after incubation, the mice were euthanized and the spleens and livers were removed for pathologic examination [26, 27]. …”

Section: Methodsmentioning

confidence: 99%

The loss-of-function mutations and down-regulated expression of ASB3 gene promote the growth and metastasis of colorectal cancer cells

Lü

et al. 2017

Chin J Cancer

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BackgroundAnkyrin repeat and SOCS box protein 3 (ASB3) is a member of ASB family and contains ankyrin repeat sequence and SOCS box domain. Previous studies indicated that it mediates the ubiquitination and degradation of tumor necrosis factor receptor 2 and is likely involved in inflammatory responses. However, its effects on oncogenesis are unclear. This study aimed to investigate the effects of ASB3 on the growth and metastasis of colorectal cancer (CRC).MethodsWe used next-generation sequencing or Sanger sequencing to detect ASB3 mutations in CRC specimens or cell lines, and used real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemical or immunofluorescence assay to determine gene expression. We evaluated cell proliferation by MTT and colony formation assays, tested cell cycle distribution by flow cytometry, and assessed cell migration and invasion by transwell and wound healing assays. We also performed nude mouse experiments to evaluate tumorigenicity and hepatic metastasis potential of tumor cells.ResultsWe found that ASB3 gene was frequently mutated (5.3%) and down-regulated (70.4%) in CRC cases. Knockdown of endogenous ASB3 expression promoted CRC cell proliferation, migration, and invasion in vitro and facilitated tumorigenicity and hepatic metastasis in vivo. Conversely, the ectopic overexpression of wild-type ASB3, but not that of ASB3 mutants that occurred in clinical CRC tissues, inhibited tumor growth and metastasis. Further analysis showed that ASB3 inhibited CRC metastasis likely by retarding epithelial-mesenchymal transition, which was characterized by the up-regulation of β-catenin and E-cadherin and the down-regulation of transcription factor 8, N-cadherin, and vimentin.Conclusion ASB3 dysfunction resulted from gene mutations or down-regulated expression frequently exists in CRC and likely plays a key role in the pathogenesis and progression of CRC.

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OTUB1 promotes metastasis and serves as a marker of poor prognosis in colorectal cancer

Cited by 77 publications

References 49 publications

Silencing of OTUB1 inhibits migration of human glioma cells in vitro

Silencing of OTUB1 inhibits migration of human glioma cells in vitro

The non‐coding RNA OTUB1‐isoform2 promotes ovarian tumour progression and predicts poor prognosis

The loss-of-function mutations and down-regulated expression of ASB3 gene promote the growth and metastasis of colorectal cancer cells

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