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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.


5′tRNA4-Val-AAC expression is associated with adverse pathology in ccRCC.Correlation of tissue small non-coding RNA levels with clinical-pathological parameters: (A) The expression of miR-122-5p was inversely correlated with M1-stage (p = 0.006), and the expression of 5′tRNA4-Val-AAC was inversely correlated with (B) less differentiated (p = 0.002) and (C) advanced (p = 0.001) ccRCC.
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f4: 5′tRNA4-Val-AAC expression is associated with adverse pathology in ccRCC.Correlation of tissue small non-coding RNA levels with clinical-pathological parameters: (A) The expression of miR-122-5p was inversely correlated with M1-stage (p = 0.006), and the expression of 5′tRNA4-Val-AAC was inversely correlated with (B) less differentiated (p = 0.002) and (C) advanced (p = 0.001) ccRCC.

Mentions: As shown in Supplementary Figure S4, we also performed qRT-PCR to determine the expression level of the full-length tRNA4-Val-AAC transcript in each 10 normal and ccRCC renal tissues. Interestingly, we did not notice any expression difference of the expression level between the normal and ccRCC tissue (p = 0.905). In contrast to this, we confirmed a significant decrease of 5′tRNA4-Val-AAC halves in ccRCC (p < 0.001). Also 5′tRNA4-Val-AAC levels were negatively correlated with tumor stage and grade: the decrease of 5′tRNA4-Val-AAC was more distinct in advanced (UICC stage III/IV vs. stage I/II: p = 0.001) and less differentiated (grade 1/2 vs. grade 3/4: p = 0.002) ccRCC. A boxplot figure indicating the expression differences is shown in Figs 3 and 4.


Identification of aberrant tRNA-halves expression patterns in clear cell renal cell carcinoma
5′tRNA4-Val-AAC expression is associated with adverse pathology in ccRCC.Correlation of tissue small non-coding RNA levels with clinical-pathological parameters: (A) The expression of miR-122-5p was inversely correlated with M1-stage (p = 0.006), and the expression of 5′tRNA4-Val-AAC was inversely correlated with (B) less differentiated (p = 0.002) and (C) advanced (p = 0.001) ccRCC.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: 5′tRNA4-Val-AAC expression is associated with adverse pathology in ccRCC.Correlation of tissue small non-coding RNA levels with clinical-pathological parameters: (A) The expression of miR-122-5p was inversely correlated with M1-stage (p = 0.006), and the expression of 5′tRNA4-Val-AAC was inversely correlated with (B) less differentiated (p = 0.002) and (C) advanced (p = 0.001) ccRCC.
Mentions: As shown in Supplementary Figure S4, we also performed qRT-PCR to determine the expression level of the full-length tRNA4-Val-AAC transcript in each 10 normal and ccRCC renal tissues. Interestingly, we did not notice any expression difference of the expression level between the normal and ccRCC tissue (p = 0.905). In contrast to this, we confirmed a significant decrease of 5′tRNA4-Val-AAC halves in ccRCC (p < 0.001). Also 5′tRNA4-Val-AAC levels were negatively correlated with tumor stage and grade: the decrease of 5′tRNA4-Val-AAC was more distinct in advanced (UICC stage III/IV vs. stage I/II: p = 0.001) and less differentiated (grade 1/2 vs. grade 3/4: p = 0.002) ccRCC. A boxplot figure indicating the expression differences is shown in Figs 3 and 4.

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.