O-GlcNAcylation of YY1 stimulates tumorigenesis in colorectal cancer cells by targeting SLC22A15 and AANAT
O-GlcNAcylation of YY1 stimulates tumorigenesis in colorectal cancer cells by targeting SLC22A15 and AANAT
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YY1 的 O-GlcNAc 酰化通过靶向 SLC22A15 和 AANAT 刺激结直肠癌细胞的肿瘤发生
DOI：
10.1093/carcin/bgz010
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发表时间：
2019
期刊：
影响因子：
4.7
通讯作者：
Sun Fenyong
中科院分区：
文献类型：
--
作者：
Zhu Guoqing;Qian Mingping;Lu Liesheng;Chen Yan;Zhang Xiao;Wu Qi;Liu Ya;Bian Zhixuan;Yang Yueyue;Guo Susu;Wang Jiayi;Pan Qiuhui;Sun Fenyong
近年来的研究表明，O-GlcNAc酰化在结直肠癌（CRC）的发生发展中起着重要作用。然而，其基本机制仍然在很大程度上是未知的。本研究证明，阴阳1号（Yin Yang 1，YY 1）被O-GlcNAc转移酶（O-GlcNAc transferase，OGT）修饰后，其蛋白质表达量增加，稳定性增强，O-GlcNAc修饰以YY 1依赖的方式促进大肠癌细胞表型的转化。此外，O-GlcNAc化刺激YY 1依赖性转录活性。此外，我们还发现了受YY 1直接调控的癌蛋白SLC 22 A15和AANAT，它们与YY 1刺激的肿瘤发生有关。此外，我们还发现YY 1的主要推测O-GlcNAc位点位于Thr 236，该位点的突变降低了YY 1的促肿瘤能力。我们的结论是YY 1的O-GlcNAc化通过靶向SLC 22 A15和AANAT刺激CRC细胞的肿瘤发生，提示YY 1 O-GlcNAc化可能是治疗CRC的潜在有效靶点。
Emerging studies have revealed thatO-GlcNAcylation plays pivotal roles in the tumorigenesis of colorectal cancers (CRCs). However, the underlying mechanism still remains largely unknown. Here, we demonstrated that Yin Yang 1 (YY1) wasO-GlcNAcylated byO-GlcNAc transferase (OGT) andO-GlcNAcylation of YY1 could increase the protein expression by enhancing its stability.O-GlcNAcylation facilitated transformative phenotypes of CRC cell in a YY1-dependent manner. Also,O-GlcNAcylation stimulates YY1-dependent transcriptional activity. Besides, we also identified the oncoproteins, SLC22A15 and AANAT, which were regulated by YY1 directly, are responsible for the YY1 stimulated tumorigenesis. Furthermore, we identified the main putativeO-GlcNAc site of YY1 at Thr236, and mutating of this site decreased the pro-tumorigenic capacities of YY1. We concluded thatO-GlcNAcylation of YY1 stimulates tumorigenesis in CRC cells by targeting SLC22A15 and AANAT, suggesting that YY1O-GlcNAcylation might be a potential effective therapeutic target for treating CRC.