Identification of tRNA-Derived Fragments Expression Profile in Breast Cancer Tissues.
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ABSTRACT:
SUBMITTER: Wang X
PROVIDER: S-EPMC6935952 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
Publications
Identification of tRNA-Derived Fragments Expression Profile in Breast Cancer Tissues.
Wang Xiaoming X Yang Yining Y Tan Xuyan X Mao Xuelian X Wei Da D Yao Yufeng Y Jiang Pan P Mo Dongping D Wang Ting T Yan Feng F
Current genomics 20190401 3
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Project description:Upon exposure to stress, tRNAs are enzymatically cleaved, yielding distinct classes of tRNA-derived fragments (tRFs), yielding distinct classes of tRFs. We identify a novel class of tRFs derived from tRNA(Glu), tRNA(Asp), tRNA(Gly), and tRNA(Tyr) that, upon induction, suppress the stability of multiple oncogenic transcripts in breast cancer cells by displacing their 3' untranslated regions (UTRs) from the RNA-binding protein YBX1. This mode of post-transcriptional silencing is sequence specific, as these fragments all share a common motif that matches the YBX1 recognition sequence. Loss-of-function and gain-of-function studies, using anti-sense locked-nucleic acids (LNAs) and synthetic RNA mimetics, respectively, revealed that these fragments suppress growth under serum-starvation, cancer cell invasion, and metastasis by breast cancer cells. Highly metastatic cells evade this tumor-suppressive pathway by attenuating the induction of these tRFs. Our findings reveal a tumor-suppressive role for specific tRNA-derived fragments and describe a molecular mechanism for their action. This transcript displacement-based mechanism may generalize to other tRNA, ribosomal-RNA, and sno-RNA fragments.
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Project description:Transfer RNA-derived fragments (tRFs) and transfer RNA halves (tiRNAs) have been shown to play crucial roles in gene regulation. This study targets to reveal the expression profile of tRFs and tiRNAs and their possible biological roles in lung adenocarcinoma (LUAD). Five paired clinical lung adenocarcinoma tissues (LAT) and adjacent normal lung tissues (ANLT) were selected to conduct the expression of tRFs and tiRNAs. The sequencing results showed that 109 tRFs and tiRNAs were differentially expressed between LAT and ANLT, out of which 60 were upregulated and 49 were downregulated. Compared with ANLT, lower expression levels of three tRF-1s (tRF-Ser-TGA-010, tRF-Arg-CCT-018 and tRF-Val-CAC-017) in LAT were verified by quantitative real-time polymerase chain reaction. Subsequently, the putative target genes of tRF-1s were analyzed by computational prediction and the top ten significant results of GO and KEGG pathway enrichment analysis were presented. These signaling pathways are involved in the carcinogenesis of LUAD. This study has showed a landscape of tRFs and tiRNAs expression profiles in LUAD. Three newly found differentially expressed down-regulated tRF-1s may be involved in the pathogenesis of LUAD and might serve as potential diagnostic biomarkers.
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