Survey of the translation shifts in hepatocellular carcinoma with ribosome profiling.,Theranostics

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Survey of the translation shifts in hepatocellular carcinoma with ribosome profiling.
Theranostics ( IF 12.4 ) Pub Date : 2019-01-01 , DOI: 10.7150/thno.35033
Qin Zou _{1,

2,

3,

4} , Zhengtao Xiao _{1,

2,

3} , Rongyao Huang _{1,

2,

3} , Xin Wang _{1,

2,

3} , Xun Wang ₅ , Haitao Zhao ₆ , Xuerui Yang _{1,

2,

3}

Affiliation

Despite the critical position of translation in the multilevel gene expression regulation program, high-resolution and genome-wide view of the landscape of RNA translation in solid tumors is still limited. Methods: With a ribosome profiling procedure optimized for solid tissue samples, we profiled the translatomes of liver tumors and their adjacent noncancerous normal liver tissues from 10 patients with hepatocellular carcinoma (HCC). A set of bioinformatics tools was then applied to these data for the mining of novel insights into the translation shifts in HCC. Results: This is the first translatome data resource for dissecting dysregulated translation in HCC at the sub-codon resolution. Based on our data, quantitative comparisons of mRNA translation rates yielded the genes and processes that were subjected to patient specific or universal dysregulations of translation efficiencies in tumors. For example, multiple proteins involved in extracellular matrix organization exhibited significant translational upregulation in tumors. We then experimentally validated the tumor-promoting functions of two such genes as examples: AGRN and VWA1. In addition, the data was also used for de novo annotation of the translatomes in tumors and normal tissues, including multiple types of novel non-canonical small ORFs, which would be a resource for further functional studies. Conclusions: The present study generates the first survey of the HCC translatome with ribosome profiling, which is an insightful data resource for dissecting the translatome shift in liver cancer, at sub-codon resolution.

中文翻译：

核糖体图分析肝细胞癌的翻译变化。

尽管翻译在多级基因表达调控程序中处于关键地位，但实体瘤中RNA翻译的高分辨率和全基因组视野仍然有限。方法：采用针对实体组织样品进行了优化的核糖体分析程序，我们对10例肝细胞癌（HCC）患者的肝肿瘤及其相邻的非癌性正常肝组织的翻译组进行了分析。然后，将一组生物信息学工具应用于这些数据，以挖掘有关HCC翻译变化的新颖见解。结果：这是第一个以亚密码子分辨率剖析HCC中翻译失调的翻译组数据资源。根据我们的数据，mRNA翻译速率的定量比较产生了基因和过程，这些基因和过程经历了患者特定或普遍的肿瘤翻译效率异常调节。例如，参与细胞外基质组织的多种蛋白质在肿瘤中表现出显着的翻译上调。然后，我们通过实验验证了两个此类基因的促肿瘤功能，例如AGRN和VWA1。此外，该数据还用于从头注释肿瘤和正常组织中的翻译组，包括多种类型的新型非规范性小ORF，这将为进一步的功能研究提供资源。结论：本研究首次对具有核糖体图谱的HCC跨膜组进行了调查，这是剖析肝癌中跨膜组移位的有见地的数据资源，

更新日期：2019-01-01

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