tRNA over-expression in breast cancer and functional consequences.
tRNA over-expression in breast cancer and functional consequences.
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DOI：
10.1093/nar/gkp787
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发表时间：
2009-11
影响因子：
14.9
通讯作者：
Pan T
中科院分区：
文献类型：
--
作者：
Pavon-Eternod M;Gomes S;Geslain R;Dai Q;Rosner MR;Pan T
增殖增加和蛋白质合成水平升高是转化细胞和肿瘤细胞的特征。虽然翻译机制的组成部分在癌症中经常被错误调节，但tRNA在癌细胞中扮演的角色尚未被探索。我们比较了癌源性乳腺细胞系与非癌源性乳腺细胞系的全基因组tRNA表达，以及乳腺肿瘤与正常乳腺组织的tRNA表达。在癌症来源的细胞系与非癌症来源的细胞系中，核编码的tRNA增加高达3倍，而细胞质编码的tRNA增加高达5倍。在肿瘤与正常乳腺组织中，细胞核和乳腺癌编码的tRNA增加高达10倍。这种tRNA过表达是选择性的，并与同源氨基酸的性质相协调。核和乳腺癌编码的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。我们还对细胞系的密码子使用-tRNA表达进行了关联分析。tRNA同功受体表达水平不适合管家或细胞系特异性基因的最佳翻译。相反，tRNA同功受体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肿瘤细胞中tRNA过表达的功能后果。tRNA同功受体的过表达可能增加与癌症发展和进展相关的基因的翻译效率。
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.
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