Long non-coding RNA SPRY4-IT1 pormotes colorectal cancer metastasis by regulate epithelial-mesenchymal transition

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.

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

Current Bioinformatics ◽

10.2174/1574893616999210805164414 ◽

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.

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