Cullin 4A (CUL4A), a direct target of miR-9 and miR-137, promotes gastric cancer proliferation and invasion by regulating the Hippo signaling pathway

Deng, Jun; Wan, Lei; Xiang, Xiaojun; Zhang, Ling; Lei, Jun; Gong, Yu; Song, Meijiao; Wang, Yi; Fang, Ziling; Yu, Feng; Mao, Feng; Sun, Ze; Chen, Jun; Zhan, Zhi-Hui; Xiong, Jianping

doi:10.18632/oncotarget.7048

Cited by 62 publications

(54 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Researchers have found that CUL4A plays a critical role in cellular proliferation and tumor invasion [36][37][38]. At the same time, our experiments in vivo and in vitro support those clinical assays.…”

Section: Discussionsupporting

confidence: 83%

See 1 more Smart Citation

High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival

Liao

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Cullin 4A (CUL4A) is vital in cell survival, development, growth and cell cycle, it plays an important role in chaperone-mediated ubiquitination and interacts with TP53 in carcinogenesis. However, the clinicopathologic significance of CUL4A expression in colorectal cancer is unknown; in particular, the prognostic value of CUL4A combined with TP53 expression has not been explored. Methods: We analyzed the expression of CUL4A in both public database (Oncomine) and 180 cases of colorectal cancer and paired normal tissues by real-time polymerase chain reaction and western blotting. Colony formation, wound healing, migration and invasion assays and tumorigenesis in nude mice were used to explore the function of CUL4A in CRC proliferation and metastasis in vitro and in vivo. Markers of epithelial to mesenchymal transition (EMT) were evaluated by western blotting. Immunohistochemistry (IHC) was used to analyse the relationship between CUL4A expression and E-cadherin expression. Results: CUL4A and TP53 protein expression was significantly higher in cancerous tissues compared to normal tissues. Significant correlation between CUL4A and TP53 expression was observed. CUL4A expression was an independent prognostic factor for overall survival (OS) and disease-free survival (DFS). Interestingly, patients with tumors that had both CUL4A overexpression and mutant TP53 protein accumulation relapsed and died within a significantly short period after surgery (P < 0.001). Multivariate analysis showed that patients with both CUL4A+ and TP53+ positive tumors had extremely poor OS and DFS. Knockdown of CUL4A by a short interfering RNA (siRNA) significantly suppressed the progression of EMT, proliferation, migration, and invasion of colon cancer cells in vitro and tumor growth in vivo. ZEB1 silencing blocked CUL4A-driven these processes. Conclusion: CUL4A expression correlated positively with the prognosis of colorectal cancer. Mechanistically, ZEB1 was confirmed to mediate the function of CUL4A in regulating the EMT. The assessment of both CUL4A and mutant TP53 expression will be helpful in predicting colon cancer prognosis.

show abstract

Section: Discussionsupporting

confidence: 83%

“…Larger prospective studies are needed to confirm our findings. Secondly, the roles of several transcription factors and non-coding RNA as EMT regulators (miR-137 and miR-9) have not been explored [37,43,44]. Thirdly, the relationship between CUL4A and TP53 has not been further explored.…”

Section: Resultsmentioning

confidence: 99%

High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival

Liao

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…In our previous study, we found that CUL4A expression was upregulated in GC tissues and cell lines and that it was associated with poor prognosis in patients with GC 30. In the present study, we also found that CUL4A expression was frequently increased in human GC tissues when compared with normal gastric tissues.…”

Section: Discussionsupporting

confidence: 80%

<em>CUL4A</em> promotes cell invasion in gastric cancer by activating the NF-κB signaling pathway

Gong

Xiang

Mao

et al. 2017

BTT

Self Cite

View full text Add to dashboard Cite

Cullin 4A (CUL4A) overexpression has been reported to be involved in the carcinogenesis and progression of many malignant tumors. However, the role of CUL4A in the progression of gastric cancer (GC) remains unclear. In this study, we explored whether and how CUL4A regulates proinflammatory signaling to promote GC cell invasion. Our results showed that knockdown of CUL4A inhibited GC cell migration and invasion induced by lipopolysaccharide (LPS) stimulation. We also found that both CUL4A and nuclear factor-kappa B (NF-κB) protein expressions were enhanced by LPS stimulation in HGC27 GC cell lines. Furthermore, knockdown of CUL4A decreased the protein expression of NF-κB and mRNA expression of the downstream genes of the NF-κB pathway, such as matrix metalloproteinase (MMP) 2, MMP9, and interleukin-8. Our immunohistochemistry analysis on 50 GC tissue samples also revealed that CUL4A positively correlated with NF-κB expression. Taken together, our findings suggest that CUL4A may promote GC cell invasion by regulating the NF-κB signaling pathway and could be considered as a potential therapeutic target in patients with GC.

show abstract

“…All scores were evaluated by two pathologists who were blinded to the pathological information. Immunohistochemical grading standards were performed according to the previously described methods …”

Section: Methodsmentioning

confidence: 99%

“…Immunohistochemistry was performed as previously described. 25 Slides were incubated with IRF2BP2 rabbit polyclonal antibody (1:100; Abcam, ab180891) in a humidified chamber overnight at 4°C, washed thrice with PBS and incubated with secondary antibody for 50 min at 37°C. Sections were washed, developed with 3,3′-diaminobenzidine tetrahydrochloride and counterstained with haematoxylin before mounting.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Down‐regulation of interferon regulatory factor 2 binding protein 2 suppresses gastric cancer progression by negatively regulating connective tissue growth factor

Yao

Wang

et al. 2019

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a transcriptional repressor involved in regulating gene expression and other biological processes, including tumorigenesis. However, the clinical significance and roles of IRF2BP2 in human gastric cancer (GC) remain uncertain. Clinical GC tissues were obtained from GC patients at the First Affiliated Hospital of Nanchang University. Immunohistochemistry (IHC) was conducted to detect the IRF2BP2 protein in clinical paraffin specimens. Cell proliferation, migration and invasion were evaluated by MTT, colony formation assays and transwell assays. Co‐immunoprecipitation was conducted to detect the interaction between TEA domain family members 4 (TEAD4) and vestigial‐like family member 4 (VGLL4) or Yes‐associated protein 1 (YAP1). Dual‐luciferase reporter assay was used to confirm the binding of miR‐101‐3p to the 3′‐UTR. The expression of IRF2BP2 was significantly higher in GC tissues than in normal tissues. Patients with higher IRF2BP2 protein expression had lower survival. IRF2BP2 knockdown inhibited proliferation, migration, invasion and epithelial‐mesenchymal transition in GC cells. IRF2BP2 knockdown decreased the mRNA and protein levels of connective tissue growth factor (CTGF). The interaction between IRF2BP2 and VGLL4 increased the binding of TEAD4 to YAP1, resulting in the transcriptional coactivation of CTGF. In addition, miR‐101‐3p suppressed the expression of CTGF by directly targeting the 3′‐UTR of IRF2BP2. Taken together, these findings provide a model for the role of miR‐101‐3p‐IRF2BP2‐CTGF signalling axis in GC and a novel insight into the mechanism of GC progression and metastasis.

show abstract

Cullin 4A (CUL4A), a direct target of miR-9 and miR-137, promotes gastric cancer proliferation and invasion by regulating the Hippo signaling pathway

Cited by 62 publications

References 52 publications

High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival

High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival

<em>CUL4A</em> promotes cell invasion in gastric cancer by activating the NF-κB signaling pathway

Down‐regulation of interferon regulatory factor 2 binding protein 2 suppresses gastric cancer progression by negatively regulating connective tissue growth factor

Contact Info

Product

Resources

About

Cullin 4A (CUL4A), a direct target of miR-9 and miR-137, promotes gastric cancer proliferation and invasion by regulating the Hippo signaling pathway

Cited by 62 publications

References 52 publications

High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival

High Expressions of CUL4A and TP53 in Colorectal Cancer Predict Poor Survival

<em>CUL4A</em> promotes cell invasion in gastric cancer by activating the NF-&kappa;B signaling pathway

Down‐regulation of interferon regulatory factor 2 binding protein 2 suppresses gastric cancer progression by negatively regulating connective tissue growth factor

Contact Info

Product

Resources

About

<em>CUL4A</em> promotes cell invasion in gastric cancer by activating the NF-κB signaling pathway