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

内部核糖体进入位点介导鼻咽癌中 Bmi1 的不依赖于帽子的翻译

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作者:Hongbo Wang, Yunjia Zhu, Lijuan Hu, Yangyang Li, Guihong Liu, Tianliang Xia, Dan Xiong, Yiling Luo, Binliu Liu, Yu An, Manzhi Li, Yuehua Huang, Qian Zhong, Musheng Zeng

Abstract

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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