From the Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013; the Key Laboratory of Carcinogenesis of the Chinese Ministry of Health, the Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, and Cancer Research Institute, Central South University, Changsha, Hunan 410078.
From the Hunan Cancer Hospital and the Affiliated Tumor Hospital of Xiangya Medical School, Central South University, Changsha, Hunan 410013.
J Biol Chem. 2019 Apr 12;294(15):6172-6187. doi: 10.1074/jbc.RA118.006281. Epub 2019 Feb 4.
Yin Yang 1 (YY1) is a zinc-finger protein that plays critical roles in various biological processes by interacting with DNA and numerous protein partners. YY1 has been reported to play dual biological functions as either an oncogene or tumor suppressor in the development and progression of multiple cancers, but its role in human nasopharyngeal carcinoma (NPC) has not yet been revealed. In this study, we found that YY1 overexpression significantly inhibits cell proliferation and cell-cycle progression from G to S and promotes apoptosis in NPC cells. Moreover, we identified YY1 as a component of the c-Myc complex and observed that ectopic expression of YY1 inhibits c-Myc transcriptional activity, as well as the promoter activity and expression of the c-Myc target gene (). Furthermore, restoring expression could at least partially reverse the inhibitory effect of YY1 on cell proliferation and tumor growth and on the expression of some critical c-Myc targets, such as PTEN/AKT pathway components both and We also found that YY1 expression is reduced in NPC tissues, negatively correlates with expression and clinical stages in NPC patients, and positively correlates with survival prognosis. Our results reveal a previously unappreciated mechanism in which the YY1/c-Myc/ axis plays a critical role in NPC progression and may provide some potential and valuable targets for the diagnosis and treatment of NPC.
阴阳 1 (YY1) 是一种锌指蛋白，通过与 DNA 和众多蛋白伴侣相互作用，在各种生物学过程中发挥关键作用。已有报道称，YY1 在多种癌症的发生和发展过程中具有双重生物学功能，既是癌基因又是肿瘤抑制因子，但它在人鼻咽癌 (NPC) 中的作用尚未被揭示。在本研究中，我们发现 YY1 过表达可显著抑制 NPC 细胞的增殖和细胞周期从 G 期向 S 期的进展，并促进细胞凋亡。此外，我们鉴定出 YY1 是 c-Myc 复合物的一个组成部分，并观察到异位表达 YY1 抑制 c-Myc 转录活性以及 c-Myc 靶基因 () 的启动子活性和表达。此外，恢复 表达至少可以部分逆转 YY1 对细胞增殖、肿瘤生长以及一些关键 c-Myc 靶基因（如 PTEN/AKT 通路成分 和 ）表达的抑制作用。我们还发现，YY1 在 NPC 组织中的表达降低，与 NPC 患者的 表达和临床分期呈负相关，与生存预后呈正相关。我们的研究结果揭示了一个以前未被认识的机制，即 YY1/c-Myc/ 轴在 NPC 的进展中起着关键作用，并且可能为 NPC 的诊断和治疗提供一些有潜力和有价值的靶点。
