scholarly journals MYB mediates downregulation of the colorectal cancer metastasis suppressor HNRNPLL during epithelial‐mesenchymal transition

2021 ◽  
Author(s):  
Keiichiro Sakuma ◽  
Eiichi Sasaki ◽  
Waki Hosoda ◽  
Koji Komori ◽  
Yasuhiro Shimizu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastasis Suppressor ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Metastasis

scholarly journals PLAGL2 promotes epithelial–mesenchymal transition and mediates colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1

2019 ◽  
Vol 122 (4) ◽  
pp. 578-589
Author(s):  
Liang Wu ◽  
Zili Zhou ◽  
Shengbo Han ◽  
Jinhuang Chen ◽  
Zhengyi Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Malignant Tumours ◽  
Mesenchymal Transition ◽  
Exact Function ◽  
Colorectal Cancer Metastasis

Abstract Background We previously demonstrated that the pleomorphic adenoma gene like-2 (PLAGL2) is involved in the pathogenesis of Hirschsprung disease. Enhanced PLAGL2 expression was observed in several malignant tumours. However, the exact function of PLAGL2 and its underlying mechanism in colorectal cancer (CRC) remain largely unknown. Methods Immunohistochemical analysis of PLAGL2 was performed. A series of in vitro and in vivo experiments were conducted to reveal the role of PLAGL2 in the progression of CRC. Results Enhanced PLAGL2 expression was significantly associated with EMT-related proteins in CRC. The data revealed that PLAGL2 promotes CRC cell proliferation, migration, invasion and EMT both in vitro and in vivo. Mechanistically, PLAGL2 promoted the expression of ZEB1. PLAGL2 enhanced the expression and nuclear translocation of β-catenin by decreasing its phosphorylation. The depletion of β-catenin neutralised the regulation of ZEB1 that was caused by enhanced PLAGL2 expression. The small-molecule inhibitor PNU-74654, also impaired the enhancement of ZEB1 that resulted from the modified PLAGL2 expression. The depletion of ZEB1 could block the biological function of PLAGL2 in CRC cells. Conclusions Collectively, our findings suggest that PLAGL2 mediates EMT to promote colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1.

Identification of Key Histone Modifications and Hub Genes for Colorectal Cancer Metastasis

2021 ◽  
Vol 16 ◽  
Author(s):  
Yuan-Yuan Zhai ◽  
Qian-Zhong Li ◽  
Ying-Li Chen ◽  
Lu-Qiang Zhang
Keyword(s):  
Colorectal Cancer ◽  
Histone Modification ◽  
Histone Modifications ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Interaction Network ◽  
Hub Genes ◽  
Mesenchymal Transition ◽  
Protein Protein Interaction ◽  
Colorectal Cancer Metastasis

Background: Epithelial-mesenchymal transition (EMT) and its reverse mesenchymal-epithelial transition (MET) are essential for tumor cells metastasis. However, the effect of epigenetic modifications on this transition is unclear. Objective: We aimed to explore the key histone modifications and hub genes of EMT/MET during colorectal cancer (CRC) metastasis. Method: The differentially expressed genes and differentially histone modified genes were identified. Based on the histone modification features, the up- and down-regulated genes were predicted by Random Forest algorithm. Through protein-protein interaction network and Cytoscape analysis, the hub genes with histone modification changes were selected. GO, KEGG and survival analysis were performed to confirm the importance of the hub genes. Results: It was found that H3K79me3 plays an important role in EMT/MET. And the 200-300bp and 400-500bp downstream of TSS may be the key regulatory regions of H3K79me3. Moreover, we found that the expression of the hub genes was down-regulated in EMT and then up-regulated in MET. And the changes of the hub genes expression were consistent with the changes of H3K79me3 signal in the specific regions of the genome. Finally, the hub genes KRT8 and KRT18 were involved in the metastasis process and were significantly related to the survival time. Conclusion: H3K79me3 may be crucial for EMT/MET, and the hub genes KRT8 and KRT18 may be the key genes in this process.

HNRNPLL, a newly identified colorectal cancer metastasis suppressor, modulates alternative splicing of CD44 during epithelial-mesenchymal transition

Gut ◽  
2017 ◽  
Vol 67 (6) ◽  
pp. 1103-1111 ◽  
Author(s):  
Keiichiro Sakuma ◽  
Eiichi Sasaki ◽  
Kenya Kimura ◽  
Koji Komori ◽  
Yasuhiro Shimizu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Cells ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Metastasis Suppressor ◽  
Colon Cancer Cells ◽  
Mesenchymal Transition ◽  
Matrigel Invasion ◽  
Shrna Library

ObjectiveDespite the recent advances in treatment of colon cancer, the prognosis is unfavourable for patients with distant metastases. The aim of this study was to identify targets for prevention and/or therapy of colon cancer metastasis.DesignCMT93 cells, a murine rectal cancer cell line with poor metastasising activity, were transduced with lentiviral shRNA library and transplanted into the rectum of syngeneic C57BL/6 mice. Genomic DNA was collected from metastatic lesions, and the integrated shRNA were retrieved by PCR for sequencing, followed by identification of the candidate genes targeted by the shRNA.ResultsThe genome-wide shRNA library screen identified Hnrnpll (heterogeneous nuclear ribonucleoprotein L-like) encoding a pre-mRNA splicing factor as a candidate metastasis suppressor gene. Knockdown of Hnrnpll enhanced matrigel invasion activity of colon cancer cells in vitro, as well as their metastatic ability in vivo. An RNA-immunoprecipitation analysis showed Hnrnpll-binding to Cd44 pre-mRNAs, and the level of Cd44 variable exon 6 (Cd44v6), a poor prognosis marker of colorectal cancer, was increased by knocking down Hnrnpll. A neutralising Cd44v6 antibody suppressed the matrigel invasion ability induced by Hnrnpll knockdown. HNRNPLL expression was downregulated when colon cancer cells were induced to undergo epithelial-mesenchymal transition (EMT). Immunohistochemistry of clinical samples indicated that colorectal cancer cells with low E-cadherin expression at the invasion front exhibited decreased HNRNPLL expression.ConclusionsHNRNPLL is a novel metastasis suppressor of colorectal cancer, and modulates alternative splicing of CD44 during EMT.

scholarly journals FOXF1 Induces Epithelial-Mesenchymal Transition in Colorectal Cancer Metastasis by Transcriptionally Activating SNAI1

Neoplasia ◽  
2018 ◽  
Vol 20 (10) ◽  
pp. 996-1007 ◽  
Author(s):  
Shuyang Wang ◽  
Shanshan Yan ◽  
Shaowei Zhu ◽  
Yali Zhao ◽  
Junyu Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Metastasis

scholarly journals Cdk3-promoted epithelial-mesenchymal transition through activating AP-1 is involved in colorectal cancer metastasis

Oncotarget ◽  
2016 ◽  
Vol 7 (6) ◽  
pp. 7012-7028 ◽  
Author(s):  
Jinping Lu ◽  
Zhen Lin Zhang ◽  
Damao Huang ◽  
Na Tang ◽  
Yuejin Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Metastasis
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