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

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


miRNA expression profiles discriminate normal and ccRCC tissue.(A) A multi dimensional scaling plot demonstrates accurate classification of 18 corresponding normal (green dots) and ccRCC (pink dots) tissue samples based on the miRNA expression profile. Distances between samples are corresponding to leading log2-fold changes between each pair of RNA samples. The leading log-fold-change is the average of the largest absolute log-fold-changes between the corresponding samples. The volcano plots are showing the expression of miRNA (B) and tRNA (C) in normal and ccRCC tissue. miRNAs/tRNAs with an at least 2-fold significant expression difference are indicated with blue dots.
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f1: miRNA expression profiles discriminate normal and ccRCC tissue.(A) A multi dimensional scaling plot demonstrates accurate classification of 18 corresponding normal (green dots) and ccRCC (pink dots) tissue samples based on the miRNA expression profile. Distances between samples are corresponding to leading log2-fold changes between each pair of RNA samples. The leading log-fold-change is the average of the largest absolute log-fold-changes between the corresponding samples. The volcano plots are showing the expression of miRNA (B) and tRNA (C) in normal and ccRCC tissue. miRNAs/tRNAs with an at least 2-fold significant expression difference are indicated with blue dots.

Mentions: sncRNA expression including miRNAs, tRNAs, piRNAs and sn(o)RNAs was profiled using small RNA sequencing. We investigated the sncRNA profile in a discovery cohort of 18 corresponding ccRCC and normal renal tissue samples. We observed differential expression (defined as log2-fold expression difference >2 and p-value < 0.05) of 132 miRNAs: 61 miRNAs were upregulated and 71 were downregulated in ccRCC. Many of these differentially expressed miRNAs have been reported before, but we also identified deregulated miRNAs not yet known to have a potential impact on ccRCC pathogenesis (e.g. miR-142-3p, miR-885-5p, miR-1910-5p, miR-186-3p, miR-4652-5p, miR-6737-3p, miR-508-5p, miR-513c-5p, miR-4485-3p, miR-513a-5p, miR-4461). A summary of the 10 most up- and downregulated miRNAs in ccRCC is provided in Table 1. As expected, miRNA expression profiles allowed precise discrimination of normal and ccRCC tissues: a multi-dimensional scaling plot identifies two clearly separable clusters of ccRCC and normal renal tissue samples, as shown in Fig. 1A. The volcano plot in Fig. 1B demonstrates the miRNA expression differences in normal and ccRCC tissue. A heatmap of miRNA expression in renal tissues is provided in Supplementary Figure S1.


Identification of aberrant tRNA-halves expression patterns in clear cell renal cell carcinoma
miRNA expression profiles discriminate normal and ccRCC tissue.(A) A multi dimensional scaling plot demonstrates accurate classification of 18 corresponding normal (green dots) and ccRCC (pink dots) tissue samples based on the miRNA expression profile. Distances between samples are corresponding to leading log2-fold changes between each pair of RNA samples. The leading log-fold-change is the average of the largest absolute log-fold-changes between the corresponding samples. The volcano plots are showing the expression of miRNA (B) and tRNA (C) in normal and ccRCC tissue. miRNAs/tRNAs with an at least 2-fold significant expression difference are indicated with blue dots.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5121638&req=5

f1: miRNA expression profiles discriminate normal and ccRCC tissue.(A) A multi dimensional scaling plot demonstrates accurate classification of 18 corresponding normal (green dots) and ccRCC (pink dots) tissue samples based on the miRNA expression profile. Distances between samples are corresponding to leading log2-fold changes between each pair of RNA samples. The leading log-fold-change is the average of the largest absolute log-fold-changes between the corresponding samples. The volcano plots are showing the expression of miRNA (B) and tRNA (C) in normal and ccRCC tissue. miRNAs/tRNAs with an at least 2-fold significant expression difference are indicated with blue dots.
Mentions: sncRNA expression including miRNAs, tRNAs, piRNAs and sn(o)RNAs was profiled using small RNA sequencing. We investigated the sncRNA profile in a discovery cohort of 18 corresponding ccRCC and normal renal tissue samples. We observed differential expression (defined as log2-fold expression difference >2 and p-value < 0.05) of 132 miRNAs: 61 miRNAs were upregulated and 71 were downregulated in ccRCC. Many of these differentially expressed miRNAs have been reported before, but we also identified deregulated miRNAs not yet known to have a potential impact on ccRCC pathogenesis (e.g. miR-142-3p, miR-885-5p, miR-1910-5p, miR-186-3p, miR-4652-5p, miR-6737-3p, miR-508-5p, miR-513c-5p, miR-4485-3p, miR-513a-5p, miR-4461). A summary of the 10 most up- and downregulated miRNAs in ccRCC is provided in Table 1. As expected, miRNA expression profiles allowed precise discrimination of normal and ccRCC tissues: a multi-dimensional scaling plot identifies two clearly separable clusters of ccRCC and normal renal tissue samples, as shown in Fig. 1A. The volcano plot in Fig. 1B demonstrates the miRNA expression differences in normal and ccRCC tissue. A heatmap of miRNA expression in renal tissues is provided in Supplementary Figure S1.

View Article: PubMed Central - PubMed

ABSTRACT

Small non-coding RNAs (sncRNA; &lt;200&thinsp;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&ndash;50&thinsp;nt) and smaller fragments (18&ndash;22&thinsp;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&ndash;24&thinsp;nt fraction, whereas tRNA reads mapped in the 30&ndash;36&thinsp;nt fraction instead the expected size of 73&ndash;95&thinsp;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&prime; cleavage of tRNAs occurs in ccRCC, but the exact functional implication of tRNA-halve deregulation remains to be clarified.

No MeSH data available.