title: Identification of aberrant tRNA-halves expression patterns in clear cell renal cell carcinoma.
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.
authors.affiliation: University Hospital Bonn, Department of Urology, Bonn, Germany.
authors.forename: Malin
authors.initials: M
authors.lastname: Nientiedt
authors.affiliation: Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.|Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.
authors.forename: Mario
authors.initials: M
authors.lastname: Deng
authors.affiliation: University Hospital Bonn, Department of Urology, Bonn, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Schmidt
authors.affiliation: Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.|Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
authors.affiliation: University Hospital Bonn, Department of Urology, Bonn, Germany.
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.affiliation: University Hospital Bonn, Department of Urology, Bonn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002292:Carcinoma, Renal Cell / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D058727:RNA, Small Untranslated / Q000378:metabolism*; D012343:RNA, Transfer / Q000378:metabolism*; D017423:Sequence Analysis, RNA
chemical_list: D035683:MicroRNAs; D058727:RNA, Small Untranslated; D012343:RNA, Transfer