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Figure 2 | BMC Medicine

Figure 2

From: Enhancer of zeste homolog 2 (EZH2) in pediatric soft tissue sarcomas: first implications

Figure 2

Possible mechanisms of deregulation of enhancer of zeste homolog 2 (EZH2) in soft tissue sarcoma (STS). (A) In normal differentiating myoblasts (left panel) promyogenic miR-26a and miR-29 are normally expressed. MiR-26a and miR-29 target EZH2 and yin yang 1 (YY1) mRNAs, respectively, at the 3' untranslated region (UTR) to induce their degradation. Conversely, in rhabdomyosarcoma (RMS) cells (right panel) promyogenic miRNAs are downregulated and their loss of function is paralleled by the overexpression of EZH2 and YY1. YY1 recruits EZH2 to repress the expression of miR-29, establishing a negative regulatory feedback loop. (B) In synovial sarcoma, the chimerical transcription factor SYT-SSX engages EZH2 that leads to H3K27 trimethylation silencing tumor suppressor genes such as early growth response 1 (EGR1). (C) In Ewing's sarcoma the chimerical transcription factor Ewing sarcoma (EWS)/Friend leukemia integration 1 (FLI1) directly contributes to the maintenance of high level of expression of EZH2.

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