CUL4B promotes bladder cancer metastasis and induces epithelial-to-mesenchymal transition by activating the Wnt/β-catenin signaling pathway

Mao, Xia-Wa; Xiao, Jiaquan; Xu, Gang; Li, Zhongyi; Wu, Huifeng; Li, Yi; Zheng, Yian; Zhang, Nan

doi:10.18632/oncotarget.20455

Cited by 31 publications

(25 citation statements)

References 27 publications

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“…The involvement of Wnt/β-catenin signalling in a wide variety of cellular processes, such as growth, differentiation, invasion and tumourigenesis (47), has been well documented. Our data, along with those of others, have revealed CUL4B to be a positive regulator of the Wnt/β-catenin pathway (9,48). In this study, based on our finding that the behaviour of GC cells was affected by miR-381, miR-489 and CUL4B expression, we examined whether the Wnt/β-catenin pathway was also involved in this interplay.…”

Section: Discussionmentioning

confidence: 58%

“…Cullin 4B (CUL4B) is a scaffold protein responsible for assembling DDB1, RBX1 and substrate component to form the CRL4B ubiquitin ligase complexes (3), contributing to ubiquitin-mediated proteolysis and tumourigenesis (4,5). Mounting evidence has highlighted the upregulation and oncogenic potential of CUL4B in various types of cancer, including hepatocellular carcinoma, lung cancer, colon cancer and bladder cancer (6)(7)(8)(9)(10). Mechanistically, CUL4B epigenetically represses a series of tumour suppressors, including insulin-like growth factor-binding protein 3 (IGFBP3), phosphatase and tensin homolog (PTEN) and p16 through physical interaction with the SIN3A/HDAC and SUV39H1/HP1/DNMT3A complexes (11,12).…”

Section: Introductionmentioning

confidence: 99%

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miR‑381 and miR‑489 suppress cell proliferation and invasion by targeting CUL4B via the Wnt/β‑catenin pathway in gastric cancer

et al. 2018

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Accumulating evidence has highlighted the critical role of cullin 4B (CUL4B) in driving tumourigenesis in several malignancies, including gastric cancer (GC); however, the mechanisms underlying CUL4B upregulation remain unclear. The dysregulation of microRNAs (miRNAs or miRs) is known to be involved in tumourigenesis. In this study, we report that the expression of miR-381 and miR-489 is downregulated and is negatively correlated with that of CUL4B in GC tissues and cell lines. Further analysis verified that miR-381 and miR-489 directly targeted CUL4B. CUL4B silencing inhibited cell proliferation, migration and invasion by inactivating the Wnt/β-catenin pathway. miR-381/miR-489 overexpression recapitulated the effects of CUL4B silencing, while CUL4B restoration negated the suppressive effects induced by the ectopic expression of miR-381/miR-489. Furthermore, miR-381/miR-489 exerted tumour suppressive functions by inactivating the Wnt/β-catenin pathway through the targeting of CUL4B. Taken together, the findings of this study suggest that the miR-381/miR-489-mediated expression of CUL4B modulates the proliferation and invasion of GC cells via the Wnt/β-catenin pathway, which indicates that the miR-381/miR-489-CUL4B axis is critical in the control of GC tumourigenesis.

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Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 99%

miR‑381 and miR‑489 suppress cell proliferation and invasion by targeting CUL4B via the Wnt/β‑catenin pathway in gastric cancer

et al. 2018

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“…Schmitz-drager et al investigated a total of 185 paraffin-embedded bladder cancer tissue specimens immunohistochemically for the overexpression of c-myc (31). Mao et al reported that activation of the Wnt/β-catenin signalling pathway induced epithelial-mesenchymal transition and promote bladder cancer metastasis (34). In addition, the Wnt signalling has been suggested as a molecular target for bladder cancer (35,36).…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA SNHG20 promotes bladder cancer via activating the Wnt/β-catenin signalling pathway

Zhao

Gao

et al. 2018

Int J Mol Med

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The long non‑coding RNA, small nucleolar RNA host gene 20 (SNHG20), is involved in promoting several common types of human cancer, however, the exact function of SNHG20 in the pathogenesis of bladder cancer remains to be elucidated. The present study aimed to examine the regulatory mechanism of SNHG20 underlying the malignant progression of bladder cancer. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to examine mRNA and protein expression. Cell survival, proliferation, apoptosis, colony formation, migration and invasion were also studied. The resulting data indicated that SNHG20 was significantly upregulated in bladder cancer tissues and cell lines, compared with its expression in adjacent non‑tumour tissues and the SV‑HUC‑1 normal urinary tract epithelial cell line, respectively. In addition, the high expression of SNHG20 was associated with advanced clinical stage, lymph node metastasis, and reduced patient survival rate. The knockdown of SNHG20 caused a significant reduction in cancer cell survival, proliferation, colony formation, migration and invasion, and induced cell apoptosis. Additionally, the inhibition of SNHG20 reduced tumour growth in vivo. Investigations into the mechanism revealed that the inhibition of SNHG20 suppressed the activation of Wnt/β‑catenin signalling and the expression of certain key genes in bladder cancer cells. Taken together, these results indicated that SNHG20 is involved in promoting bladder cancer and may be used as a potential therapeutic target for the treatment of this disease.

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“…In addition, silencing of CUL4B is also involved in cell growth. Different cell experiments had confirmed that CUL4B activates the expression of mRNA and protein levels of c-Myc, promoting Wnt/β-catenin signaling activation and tumor progression ultimately [40,41]. Investigation of DLBCL consistently illustrated the connection between Ki-67, c-Myc and aggressive clinical behavior [42][43][44].…”

Section: Discussionmentioning

confidence: 99%

CUL4B regulates autophagy via JNK signaling in diffuse large B-cell lymphoma

Zhou

Zhang

et al. 2019

Cell Cycle

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Aberrant expression of CUL4B was identified in various types of solid cancers. Cumulative evidences support the oncogenic role of CUL4B in cancers, including regulation of cell proliferation and signal transduction. However, its clinical value and potential pathogenic mechanism in diffuse large B-cell lymphoma (DLBCL) have not been described previously. Therefore, we hypothesize that overexpressed CUL4B may contribute to the pathogenesis of DLBCL. The aim of this study is to assess the expression and the biological function of CUL4B in DLBCL progression. In our study, CUL4B overexpression was observed in DLBCL tissues, and its upregulation was closely associated with poor prognosis in patients. Furthermore, the functional roles of CUL4B was detected both in vitro and in vivo. We demonstrated that silencing CUL4B could not only induce cell proliferation inhibition, cell cycle arrest, and motility attenuation of DLBCL cells in vitro, but also decrease tumor growth in DLBCL xenografts mice. In addition, we identified that CUL4B may act as a potent inductor of JNK phosphorylation in regulation of autophagy. Our findings demonstrated a significant role of CUL4B in the development and progression of DLBCL. CUL4B may act as a useful biomarker and a novel therapeutic target in DLBCL. ARTICLE HISTORY

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CUL4B promotes bladder cancer metastasis and induces epithelial-to-mesenchymal transition by activating the Wnt/β-catenin signaling pathway

Cited by 31 publications

References 27 publications

miR‑381 and miR‑489 suppress cell proliferation and invasion by targeting CUL4B via the Wnt/β‑catenin pathway in gastric cancer

miR‑381 and miR‑489 suppress cell proliferation and invasion by targeting CUL4B via the Wnt/β‑catenin pathway in gastric cancer

Long non-coding RNA SNHG20 promotes bladder cancer via activating the Wnt/β-catenin signalling pathway

CUL4B regulates autophagy via JNK signaling in diffuse large B-cell lymphoma

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