Altered expression spectrum and target gene prediction of tRNA-derived small RNAs in clear cell renal cell carcinoma.
Shuai Liu, Heng Cao, Bowen Chen, Lei Jiang, Yimingniyizi Nueraihemaiti, Yuchen Gao, Xiangcheng Zhan, Yanhua Chen, Hongmin Zhou, Ding Liu, Hao Chen, Xiao Xu, Tiancheng Xie, Wangli Mei, Yunze Dong
Abstract
Open AccessBACKGROUND: Dysregulation of tRNA-derived small RNAs (tsRNAs) in various cancers has been indicated to play vital roles in tumorigenesis, but few reported in clear cell renal cell carcinoma (ccRCC). Here, we determined to elucidate the role of tsRNAs in ccRCC and their potential as new tumor biomarkers. METHODS: We obtained the tsRNA expression spectrum of ccRCC by a small RNA microarray sequence. Eight dysregulated tsRNAs were selected and validated by reverse transcription-quantitative real-time PCR (RT-qPCR). We identified these tsRNAs' potential target genes. The biological functions of tsRNAs were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) assay. RESULTS: The microarray sequence result shown statistically significantly 433 up-regulated tsRNAs and 798 down-regulated tsRNAs in ccRCC. Then, eight tsRNAs were validated by RT-qPCR and the target genes of the validated tsRNAs were predicted by TargetScan and miRanda databases. GO annotation and KEGG pathway enrichment analyses shown that potential biological functions and signaling pathways of the predicted target genes of tsRNAs in ccRCC. The results of external databases validation suggests that tRF5-23-ValAAC-2 may be a key biomarker for ccRCC development. The functional assays revealed that tRF5-23-ValAAC-2 hinders the proliferation and migration while promotes apoptosis of ccRCC. CONCLUSIONS: In this study, we identified the tsRNA spectrum in ccRCC tissues and found that dysregulated tsRNAs may be novel biomarkers and possible therapeutic targets for ccRCC.