SNX16 activates c-Myc signaling by inhibiting ubiquitin-mediated proteasomal degradation of eEF1A2 in colorectal cancer development
SNX16 activates c-Myc signaling by inhibiting ubiquitin-mediated proteasomal degradation of eEF1A2 in colorectal cancer development
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SNX16 通过抑制结直肠癌发展中泛素介导的 eEF1A2 蛋白酶体降解来激活 c-Myc 信号传导
DOI：
10.1002/1878-0261.12626
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发表时间：
2020-01-10
影响因子：
6.6
通讯作者：
Deng, Haijun
中科院分区：
文献类型：
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作者：
Shen, Zhiyong;Li, Yongsheng;Deng, Haijun
排序连接蛋白16 （SNX16）是排序连接蛋白家族的一员，参与肿瘤的发生。然而，SNX16在结直肠癌（CRC）中的功能尚未被研究。在这里，我们发现与正常组织相比，SNX16在结直肠癌组织中的表达显著上调。SNX16 mRNA水平上调预示着结直肠癌患者的不良生存率。功能实验表明，SNX16在体外和体内均能促进结直肠癌细胞的生长。敲低SNX16可诱导细胞周期阻滞和凋亡，而异位过表达SNX16则具有相反的作用。机制上，snx16 -真核翻译延伸因子1A2 （eEF1A2）相互作用可以抑制eEF1A2的降解和泛素化，进而激活下游的c-Myc信号。我们的研究揭示了SNX16/eEF1A2/c-Myc信号轴可以促进结直肠癌的发生，SNX16可能作为CRC诊断和干预的一种新的生物标志物。
Sorting nexin 16 (SNX16), a member of the sorting nexin family, has been implicated in tumor development. However, the function of SNX16 has not yet been investigated in colorectal cancer (CRC). Here, we showed that SNX16 expression was significantly upregulated in CRC tissues compared with normal counterparts. Upregulated mRNA levels of SNX16 predicted poor survival of CRC patients. Functional experiments showed that SNX16 could promote CRC cells growth both in vitro and in vivo. Knockdown of SNX16 induced cell cycle arrest and apoptosis, whereas ectopic overexpression of SNX16 had the opposite effects. Mechanistically, SNX16-eukaryotic translation elongation factor 1A2 (eEF1A2) interaction could inhibit the degradation and ubiquitination of eEF1A2, followed by activation of downstream c-Myc signaling. Our study unveiled that the SNX16/eEF1A2/c-Myc signaling axis could promote colorectal tumorigenesis and SNX16 might potentially serve as a novel biomarker for the diagnosis and an intervention of CRC.