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.
Highlights
Renal cell carcinoma (RCC) is the most frequent renal malignancy accounting for 80–85% of the primary renal tumors
Among several deregulated tRNA, we identified 5′tRNA4-Val-AAC as downregulated in clear cell renal cell carcinoma (ccRCC), and its expression was correlated with advanced stage and grade
We investigated the small non-coding RNAs (sncRNA) profile in a discovery cohort of 18 corresponding ccRCC and normal renal tissue samples
Summary
Renal cell carcinoma (RCC) is the most frequent renal malignancy accounting for 80–85% of the primary renal tumors. The incidence of RCC is still increasing, especially the number of young patients and high-grade disease is rising[1]. The increasing number of small renal tumors may be explained by the widespread use of abdominal ultrasonography for check-up or clarification of non-specific symptoms. Small tumors are often growing slowly and active surveillance are alternative treatment options getting an increased acceptance in selected patients[5]. MiRNA, as a subclass of sncRNA, expression profiles have been established in RCCs7, and the detection of miRNAs in bodily fluids allows their use as non-invasive biomarker for patients with urological malignancies[8]. To improve the understanding of such interactions, we determined the expression profile of sncRNAs in clear cell renal cell carcinoma (ccRCC). Among several deregulated tRNA, we identified 5′tRNA4-Val-AAC as downregulated in ccRCC, and its expression was correlated with advanced stage and grade
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