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      The Emerging Function and Promise of tRNA-Derived Small RNAs in Cancer

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          Abstract

          Fragments derived from tRNA, called tRNA-derived small RNAs (tsRNAs), have attracted widespread attention in the past decade. tsRNAs are widespread in prokaryotic and eukaryotic transcriptome, which contains two main types, tRNA-derived fragments (tRFs) and tRNA-derived stress-inducing RNA (tiRNAs), derived from the precursor tRNAs or mature tRNAs. According to differences in the cleavage position, tRFs can be divided into tRF-1, tRF-2, tRF-3, tRF-5, and i-tRF, whereas tiRNAs can be divided into 5'-tiRNA and 3'-tiRNA. Studies have found that tRFs and tiRNAs are abnormally expressed in a variety of human malignant tumors, promote or inhibit the proliferation and apoptosis of cancer cells by regulating the expression of oncogene, and play an important role in the aggressive metastasis and progression of tumors. This article reviews the biological origins of various tsRNAs, introduces their functions and new concepts of related mechanisms, and focuses on the molecular mechanisms of tsRNAs in cancer, including breast cancer, prostate cancer, colorectal cancer, lung cancer, b-cell lymphoma, and chronic lymphoma cell leukemia. Lastly, this article puts forward some unresolved problems and future research prospects.

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          Most cited references140

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          MODOMICS: a database of RNA modification pathways. 2017 update

          Abstract MODOMICS is a database of RNA modifications that provides comprehensive information concerning the chemical structures of modified ribonucleosides, their biosynthetic pathways, the location of modified residues in RNA sequences, and RNA-modifying enzymes. In the current database version, we included the following new features and data: extended mass spectrometry and liquid chromatography data for modified nucleosides; links between human tRNA sequences and MINTbase - a framework for the interactive exploration of mitochondrial and nuclear tRNA fragments; new, machine-friendly system of unified abbreviations for modified nucleoside names; sets of modified tRNA sequences for two bacterial species, updated collection of mammalian tRNA modifications, 19 newly identified modified ribonucleosides and 66 functionally characterized proteins involved in RNA modification. Data from MODOMICS have been linked to the RNAcentral database of RNA sequences. MODOMICS is available at http://modomics.genesilico.pl.
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            MicroRNA signatures in human cancers.

            MicroRNA (miRNA) alterations are involved in the initiation and progression of human cancer. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the miRNA processing machinery. MiRNA-expression profiling of human tumours has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify miRNA genes that might represent downstream targets of activated oncogenic pathways, or that target protein-coding genes involved in cancer.
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              Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder.

              Increasing evidence indicates that metabolic disorders in offspring can result from the father's diet, but the mechanism remains unclear. In a paternal mouse model given a high-fat diet (HFD), we showed that a subset of sperm transfer RNA-derived small RNAs (tsRNAs), mainly from 5' transfer RNA halves and ranging in size from 30 to 34 nucleotides, exhibited changes in expression profiles and RNA modifications. Injection of sperm tsRNA fractions from HFD males into normal zygotes generated metabolic disorders in the F1 offspring and altered gene expression of metabolic pathways in early embryos and islets of F1 offspring, which was unrelated to DNA methylation at CpG-enriched regions. Hence, sperm tsRNAs represent a paternal epigenetic factor that may mediate intergenerational inheritance of diet-induced metabolic disorders.
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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2024
                27 January 2024
                : 15
                : 6
                : 1642-1656
                Affiliations
                [1 ]College of Resources, Environment and Chemistry, Chuxiong Normal University, Chuxiong 675000, China.
                [2 ]College of Basic Medical Sciences, Dali University, Dali 671000, China.
                [3 ]College of Foreign Languages, Chuxiong Normal University, Chuxiong 675000, China.
                [4 ]The People's Hospital of ChuXiong Yi Autonomous Prefecture, Chuxiong 675000, China.
                Author notes

                † These authors contributed equally to this work.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav15p1642
                10.7150/jca.89219
                10869971
                38370372
                9101a5a9-72b3-4a8b-a0f0-b4bb7595c36d
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 1 December 2023
                : 1 January 2024
                Categories
                Review

                Oncology & Radiotherapy
                tsrnas,trf,tirna,cancer,molecular mechanisms
                Oncology & Radiotherapy
                tsrnas, trf, tirna, cancer, molecular mechanisms

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