Wang Hongbo, Zhu Yunjia, Hu Lijuan, Li Yangyang, Liu Guihong, Xia Tianliang, Xiong Dan, Luo Yiling, Liu Binliu, An Yu, Li Manzhi, Huang Yuehua, Zhong Qian, Zeng Musheng
Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Front Oncol. 2020 Sep 8;10:1678. doi: 10.3389/fonc.2020.01678. eCollection 2020.
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.
Bmi1在多种人类癌症中过表达。我们之前报道了Bmi1在鼻咽癌（NPC）中的致癌功能及转录调控机制。在本研究中，我们观察到在NPC细胞系和癌组织中，Bmi1的mRNA水平和蛋白质水平并不完全一致。蛋白酶体和溶酶体抑制剂并不能提高Bmi1的蛋白质水平，这表明Bmi1可能受到转录后调控。IRESite分析显示，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（IRESs）。荧光素酶检测表明，Bmi1的5'-UTR具有IRES活性，可能介导不依赖帽子结构的翻译。两个IRES元件发生突变后，Bmi1 5'-UTR的IRES活性显著降低。综上所述，这些结果表明介导翻译的IRES元件是Bmi1一种新的转录后调控机制。
