Autoregulatory feedback loop of EZH2/miR-200c/E2F3 as a driving force for prostate cancer development.

The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has recently attracted considerable attention because of its dysregulation in prostate cancer (PCa) and its important function in PCa development. To date, little is known about the underlying cellular function and regulatory networks of EZH2 in PCa. This study aims to determine whether or not the autoregulatory feedback loop of EZH2/miR-200c/E2F3 serves key functions in PCa development. Bioinformatics and integrative analytical approaches were employed to identify the relationships of EZH2 to specific cancer-related gene sets. Results indicated that the enrichment of gene sets about cell cycle progression was associated with EZH2 expression. The depletion of EZH2 in cell experiments inhibited PCa cell growth and blocked cell cycle accompanying the downregulation of E2F3 expression. Furthermore, miR-200c served as an important mediator between EZH2 and E2F3. Compared with scrambled control cells, sh-EZH2 cells showed lower H3K27me3 expression and higher miR-200c expression. Western blot and luciferase reporter assays showed that miR-200c inversely modulated E2F3 by directly targeting the binding site within 3'UTR. Moreover, decreased miR-200c expression largely abrogated the effect of sh-EZH2 on E2F3 expression and E2F3-induced cell cycle progression. EZH2 was positively regulated by E2F3 at the transcriptional level. Immunohistochemistry and in situ hybridization revealed a significant correlation among EZH2, miR-200c, and E2F3 expression in human PCa tissues. In conclusion, the autoregulatory feedback loop of EZH2/miR-200c/E2F3 served an important function in PCa development. Targeting this aberrantly activated feedback loop may provide a new therapeutic strategy against PCa.

Tao T ，Liu D ，Liu C ，Xu B ，Chen S ，Yin Y ，Ang L ，Huang Y ，Zhang X ，Chen M ... -  《-》

Involvement of aberrantly activated HOTAIR/EZH2/miR-193a feedback loop in progression of prostate cancer.

Ling Z ，Wang X ，Tao T ，Zhang L ，Guan H ，You Z ，Lu K ，Zhang G ，Chen S ，Wu J ，Qian J ，Liu H ，Xu B ，Chen M ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

Involvement of EZH2 in aerobic glycolysis of prostate cancer through miR-181b/HK2 axis.

Tao T ，Chen M ，Jiang R ，Guan H ，Huang Y ，Su H ，Hu Q ，Han X ，Xiao J ... -  《-》

MicroRNA-101 inhibits human hepatocellular carcinoma progression through EZH2 downregulation and increased cytostatic drug sensitivity.

Oncogene polycomb group protein enhancer of zeste homolog 2 (EZH2) has been proposed to be a target gene of putative tumor suppressor microRNA-101 (miR-101). The aim of our study was to investigate the functional role of both miR-101 and EZH2 in human hepatocellular carcinoma (HCC). MiR-101 and EZH2 expressions were evaluated in tumor tissues of 99 HCC patients and 7 liver cancer cell lines by real-time PCR. Luciferase reporter assay was employed to validate whether EZH2 represents a target gene of miR-101. The effect of miR-101 on HCC growth as well as programmed cell death was studied in vitro and in vivo. MiR-101 expression was significantly downregulated in most of HCC tissues and all cell lines, whereas EZH2 was significantly overexpressed in most of HCC tissues and all cell lines. There was a negative correlation between expression levels of miR-101 and EZH2. Luciferase assay results confirmed EZH2 as a direct target gene of miR-101, which negatively regulates EZH2 expression in HCC. Ectopic overexpression of miR-101 dramatically repressed proliferation, invasion, colony formation as well as cell cycle progression in vitro and suppressed tumorigenicity in vivo. Furthermore, miR-101 inhibited autophagy and synergized with either doxorubicin or fluorouracil to induce apoptosis in tumor cells. Tumor suppressor miR-101 represses HCC progression through directly targeting EZH2 oncogene and sensitizes liver cancer cells to chemotherapeutic treatment. Our findings provide significant insights into molecular mechanisms of hepatocarcinogenesis and may have clinical relevance for the development of novel targeted therapies for HCC.

Xu L ，Beckebaum S ，Iacob S ，Wu G ，Kaiser GM ，Radtke A ，Liu C ，Kabar I ，Schmidt HH ，Zhang X ，Lu M ，Cicinnati VR ... -  《-》

Reciprocal negative feedback loop between EZH2 and miR-101-1 contributes to miR-101 deregulation in hepatocellular carcinoma.

Huang D ，Wang X ，Zhuang C ，Shi W ，Liu M ，Tu Q ，Zhang D ，Hu L ... -  《-》