Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin, Italy.
Cancer Res. 2019 Jun 15;79(12):3031-3033. doi: 10.1158/0008-5472.CAN-19-0927.
STAT3 can mediate epigenetic silencing of tumor suppressor genes (TSG). However, little is known about the molecular mechanisms involved, except that this action is mediated by DNA methylation and requires STAT3 acetylation. In this issue of , Gambi and colleagues confirm that oncogene-driven constitutive STAT3 acetylation is responsible for TSG silencing. Furthermore, they show that the Sin3a transcriptional repressor complex is an obligatory partner of STAT3 on the promoters of the repressed genes, shedding light on the mechanisms involved in STAT3-mediated transcriptional repression, and more importantly, identifying that the STAT3-Sin3a axis is a potential selective therapeutic target in STAT3-dependent tumors..
STAT3 可以介导肿瘤抑制基因 (TSG) 的表观遗传沉默。然而，除了这种作用是由 DNA 甲基化介导且需要 STAT3 乙酰化外，目前对涉及的分子机制知之甚少。在本期 杂志中，Gambi 及其同事证实，癌基因驱动的 STAT3 持续乙酰化导致 TSG 沉默。此外，他们还表明，Sin3a 转录抑制复合物是受抑制基因启动子上 STAT3 的必需伴侣，揭示了 STAT3 介导的转录抑制涉及的机制，更重要的是，确定 STAT3-Sin3a 轴是 STAT3 依赖性肿瘤的潜在选择性治疗靶点。
