Internal Ribosome Entry Sites Mediate Cap-Independent Translation of Bmi1 in Nasopharyngeal Carcinoma.

Internal Ribosome Entry Sites Mediate Cap-Independent Translation of Bmi1 in Nasopharyngeal Carcinoma.
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内部核糖体进入位点介导鼻咽癌中 Bmi1 的帽独立翻译

DOI:
10.3389/fonc.2020.01678
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发表时间:
2020
影响因子:
4.7
通讯作者:
Zeng M
Zeng M
中科院分区:
医学3区
文献类型:
--
作者:
Wang H;Zhu Y;Hu L;Li Y;Liu G;Xia T;Xiong D;Luo Y;Liu B;An Y;Li M;Huang Y;Zhong Q;Zeng M

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Bmi1 在多种人类癌症中过度表达。我们之前报道了Bmi1在鼻咽癌(NPC)中的致癌功能和转录调控机制。在本研究中,我们观察到Bmi1的mRNA和蛋白水平在鼻咽癌细胞系和癌组织中严格不一致。蛋白酶体和溶酶体抑制剂不能提高Bmi1的蛋白水平,表明Bmi1可能受到转录后调控。 IRESite分析表明,Bmi1的5′非翻译区(5′-UTR)存在两个潜在的内部核糖体进入位点(IRES)。荧光素酶测定表明 Bmi1 的 5'-UTR 具有 IRES 活性,这可能介导帽独立翻译。两个IRES元件突变后,Bmi1 5'-UTR的IRES活性显着降低。综上所述,这些结果表明介导翻译的 IRES 元件是 Bmi1 的一种新型转录后调节机制。
Bmi1 is overexpressed in multiple human cancers. We previously reported the oncogenic function and the transcription regulation mechanisms of Bmi1 in nasopharyngeal carcinoma (NPC). In this study, we observed that the mRNA and the protein levels of Bmi1 were strictly inconsistent in NPC cell lines and cancer tissues. The inhibitors of proteasome and lysosome could not enhance the protein level of Bmi1, indicating that Bmi1 may be post-transcriptionally regulated. The IRESite analysis showed that there were two potential internal ribosome entry sites (IRESs) in the 5′-untranslated region (5′-UTR) of Bmi1. The luciferase assay demonstrated that the 5′-UTR of Bmi1 has IRES activity, which may mediate cap-independent translation. The IRES activity of the Bmi1 5′-UTR was significantly reduced after the mutation of the two IRES elements. Taken together, these results suggested that the IRES elements mediating translation is a novel post-transcriptional regulation mechanism of Bmi1.
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