Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL 60637, USA.
Nucleic Acids Res. 2009 Nov;37(21):7268-80. doi: 10.1093/nar/gkp787.
Increased proliferation and elevated levels of protein synthesis are characteristics of transformed and tumor cells. Though components of the translation machinery are often misregulated in cancers, what role tRNA plays in cancer cells has not been explored. We compare genome-wide tRNA expression in cancer-derived versus non-cancer-derived breast cell lines, as well as tRNA expression in breast tumors versus normal breast tissues. In cancer-derived versus non-cancer-derived cell lines, nuclear-encoded tRNAs increase by up to 3-fold and mitochondrial-encoded tRNAs increase by up to 5-fold. In tumors versus normal breast tissues, both nuclear- and mitochondrial-encoded tRNAs increase up to 10-fold. This tRNA over-expression is selective and coordinates with the properties of cognate amino acids. Nuclear- and mitochondrial-encoded tRNAs exhibit distinct expression patterns, indicating that tRNAs can be used as biomarkers for breast cancer. We also performed association analysis for codon usage-tRNA expression for the cell lines. tRNA isoacceptor expression levels are not geared towards optimal translation of house-keeping or cell line specific genes. Instead, tRNA isoacceptor expression levels may favor the translation of cancer-related genes having regulatory roles. Our results suggest a functional consequence of tRNA over-expression in tumor cells. tRNA isoacceptor over-expression may increase the translational efficiency of genes relevant to cancer development and progression.
细胞增殖和蛋白质合成水平升高是转化和肿瘤细胞的特征。尽管翻译机制的成分在癌症中经常失调，但 tRNA 在癌细胞中的作用尚未得到探索。我们比较了癌症来源的与非癌症来源的乳腺细胞系中的全基因组 tRNA 表达，以及乳腺肿瘤与正常乳腺组织中的 tRNA 表达。在癌症来源的与非癌症来源的细胞系中，核编码 tRNA 增加了多达 3 倍，线粒体编码 tRNA 增加了多达 5 倍。在肿瘤与正常乳腺组织中，核编码和线粒体编码的 tRNA 均增加了多达 10 倍。这种 tRNA 的过度表达是选择性的，并与同源氨基酸的特性相协调。核编码和线粒体编码的 tRNA 表现出不同的表达模式，表明 tRNA 可用作乳腺癌的生物标志物。我们还针对细胞系的密码子使用- tRNA 表达进行了关联分析。tRNA 同工受体的表达水平不是针对管家基因或细胞系特异性基因的最佳翻译进行调整的。相反，tRNA 同工受体的表达水平可能有利于具有调节作用的癌症相关基因的翻译。我们的研究结果表明，tRNA 在肿瘤细胞中的过度表达具有功能后果。tRNA 同工受体的过度表达可能会增加与癌症发生和发展相关基因的翻译效率。
