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Abstract：
The alteration of RNA modification patterns is emerging as a common feature of human malignancies. If these changes affect key RNA molecules for mRNA translation, such as transfer RNA, they can have important consequences for cell transformation. TRIT1 is the enzyme responsible for the hypermodification of adenosine 37 in the anticodon region of human tRNAs containing serine and selenocysteine. Herein, we show that TRIT1 undergoes gene amplification-associated overexpression in cancer cell lines and primary samples of small-cell lung cancer. From growth and functional standpoints, the induced depletion of TRIT1 expression in amplified cells reduces their tumorigenic potential and downregulates the selenoprotein transcripts. We observed that TRIT1-amplified cells are sensitive to arsenic trioxide, a compound that regulates selenoproteins, whereas reduction of TRIT1 levels confers loss of sensitivity to the drug. Overall, our results indicate a role for TRIT1 as a small-cell lung cancer-relevant gene that, when undergoing gene amplification-associated activation, can be targeted with the differentiation agent arsenic trioxide.
摘要：
RNA修饰模式的改变正在成为人类恶性肿瘤的共同特征。如果这些变化影响mRNA翻译的关键RNA分子，例如转移RNA，它们会对细胞转化产生重要影响。TRIT1是在含有丝氨酸和硒代半胱氨酸的人tRNA的反密码子区域中负责腺苷37的超修饰的酶。在这里，我们显示TRIT1在癌细胞系和小细胞肺癌原发样本中经历了基因扩增相关的过表达.从增长和功能的角度来看，在扩增细胞中TRIT1表达的诱导缺失降低了它们的致瘤潜能并下调硒蛋白转录本。我们观察到TRIT1扩增的细胞对三氧化二砷敏感，一种调节硒蛋白的化合物，而TRIT1水平的降低会导致对药物的敏感性丧失。总的来说,我们的结果表明，TRIT1作为小细胞肺癌相关基因的作用，当经历基因扩增相关的激活时，可以用分化剂三氧化二砷靶向。
