Identification of aberrant tRNA-halves expression patterns in clear cell renal cell carcinoma.

Identification of aberrant tRNA-halves expression patterns in clear cell renal cell carcinoma.
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DOI:
10.1038/srep37158
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发表时间:
2016-11-24
期刊:
影响因子:
4.6
通讯作者:
Ellinger J
Ellinger J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nientiedt M;Deng M;Schmidt D;Perner S;Müller SC;Ellinger J

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小的非编码RNA(sncRNA; <200 nt)调节各种细胞过程并修饰基因表达。在营养、生物或生理化学胁迫下,一些成熟的sncRNA(例如tRNA)被切割成两半(30-50 nt)和更小的片段(18-22 nt);这些tRNA片段的意义和功能作用尚不清楚,但它们的存在与致癌作用有关。我们使用小RNA测序来确定sncRNA的表达。随后,使用qPCR对miR-122- 5 p、miR-142- 3 p和5 'tRNA 4-Val-AAC的发现进行验证。我们鉴定了132个miRNA(上调:61个,下调:71个)和32个tRNA(上调:13个,下调:19个)的差异表达。读取长度分析显示,miRNA定位在20-24 nt部分中,而tRNA读取定位在30-36 nt部分中,而不是预期的73-95 nt大小,从而表明tRNA的切割。在118例ccRCC和74例正常肾组织的独立队列中验证了miR-122- 5 p和miR-142- 3 p的过表达以及5 'tRNA 4-Val-AAC的下调。此外,分期和分级与5 'tRNA 4-Val-AAC表达呈负相关。在ccRCC和对照受试者中,miR-122- 5 p、miR-142- 3 p和5 'tRNA 4-Val-AAC的血清水平没有差异。总之,在ccRCC中发生了tRNA的5′切割,但tRNA半失调的确切功能含义仍有待澄清。
Small non-coding RNAs (sncRNA; <200 nt) regulate various cellular processes and modify gene expression. Under nutritional, biological or physiochemical stress some mature sncRNAs (e.g. tRNAs) are cleaved into halves (30–50 nt) and smaller fragments (18–22 nt); the significance and functional role of these tRNA fragments is unknown, but their existence has been linked to carcinogenesis. We used small RNA sequencing to determine the expression of sncRNAs. Subsequently the findings were validated for miR-122-5p, miR-142-3p and 5'tRNA4-Val-AAC using qPCR. We identified differential expression of 132 miRNAs (upregulated: 61, downregulated: 71) and 32 tRNAs (upregulated: 13, downregulated: 19). Read length analysis showed that miRNAs mapped in the 20–24 nt fraction, whereas tRNA reads mapped in the 30–36 nt fraction instead the expected size of 73–95 nt thereby indicating cleavage of tRNAs. Overexpression of miR-122-5p and miR-142-3p as well as downregulation of 5'tRNA4-Val-AAC was validated in an independent cohort of 118 ccRCC and 74 normal renal tissues. Furthermore, staging and grading was inversely correlated with the 5'tRNA4-Val-AAC expression. Serum levels of miR-122-5p, miR-142-3p and 5'tRNA4-Val-AAC did not differ in ccRCC and control subjects. In conclusion, 5′ cleavage of tRNAs occurs in ccRCC, but the exact functional implication of tRNA-halve deregulation remains to be clarified.
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