Downregulation of Enhancer of Zeste Homolog 2 (EZH2) is essential for the Induction of Autophagy and Apoptosis in Colorectal Cancer Cells
| Autor: | Xinguo Zhu, Yong Yang, Guoqiang Zhou, Xiaodong Yang, Zheng-Yuan Yu, Kang Sun, Songbing He, Shenghua Zhan, Zengfu Shang, Hao Hu, Guofeng Pan, Peiyao Li, Yizhou Yao, Liang Sun |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
autophagy lcsh:QH426-470 apoptosis colorectal cancer macromolecular substances DZNep Biology medicine.disease_cause Article 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation shRNA EZH2 Genetics medicine Genetics (clinical) Gene knockdown Autophagy Transfection Cell cycle Cell biology lcsh:Genetics 030104 developmental biology Apoptosis 030220 oncology & carcinogenesis Cancer research Carcinogenesis |
| Zdroj: | Genes Genes; Volume 7; Issue 10; Pages: 83 Genes, Vol 7, Iss 10, p 83 (2016) |
| ISSN: | 2073-4425 |
| Popis: | Increasing evidence indicates that elevated expression of enhancer of zeste homolog 2 gene (EZH2) in many human malignant tumors acts a significant role in the oncogenic process. However, the underlying molecular mechanism is still unclarified. It is evident that apoptosis and autophagy of tumor cells is crucial for the tumorigenesis and progression of cancer, however, the exact role of EZH2 plays in apoptosis and autophagy has not been fully elucidated in colorectal cancer (CRC). Our previous study found that the expression level of EZH2 was higher in CRC tumor tissues than in the paired normal tissues using immunohistochemical analysis. We also recently found that the autophagy‐related gene‐related protein Ambra1 plays an important role in the autophagy pathway in CRC cells. In this study, mRNA and protein expression of EZH2 in four CRC cell lines were tested at first and RKO and HCT116 cells showed the highest levels among them. Here we transfected with EZH2‐shRNA, or added DZNep (an EZH2 inhibitor) to RKO and HCT116 cells in order to detect the effect of EZH2 on autophagy via determining the change of the protein expression of LC3 and Ambra1. The outcome indicated an obvious decrease of autophagy level in cells transfected with EZH2‐shRNA or DZNep. We also found the apoptotic rate of cells was elevated significantly after downregulation of EZH2. In addition, compared to control group, CRC cells transfected with EZH2‐shRNA or added DZNep revealed a significantly increased G1 cell cycle rate and an obvious decrease in the G2 cell cycle rate. Further analysis showed that knockdown of EZH2 induced cell-cycle arrest in CRC cells. Meanwhile, downregulation of EZH2 in CRC cells induces autophagy and apoptosis. Taken together, our results suggest that EZH2 plays a critical role in autophagy and apoptosis in the progression of CRC, which potentially facilitates the development of an ideal strategy for combating colorectal cancer. |
| Databáze: | OpenAIRE |
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