tRNA-derived RNA fragments in cancer: current status and future perspectives
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(2020) 13:121
REVIEW
Open Access
tRNA-derived RNA fragments in cancer: current status and future perspectives Mengqian Yu1, Bingjian Lu2, Jisong Zhang1, Jinwang Ding3, Pengyuan Liu1,4 and Yan Lu2*
Abstract Non-coding RNAs (ncRNAs) have been the focus of many studies over the last few decades, and their fundamental roles in human diseases have been well established. Transfer RNAs (tRNAs) are housekeeping ncRNAs that deliver amino acids to ribosomes during protein biosynthesis. tRNA fragments (tRFs) are a novel class of small ncRNAs produced through enzymatic cleavage of tRNAs and have been shown to play key regulatory roles similar to microRNAs. Development and application of high-throughput sequencing technologies has provided accumulating evidence of dysregulated tRFs in cancer. Aberrant expression of tRFs has been found to participate in cell proliferation, invasive metastasis, and progression in several human malignancies. These newly identified functional tRFs also have great potential as new biomarkers and therapeutic targets for cancer treatment. In this review, we focus on the major biological functions of tRFs including RNA silencing, translation regulation, and epigenetic regulation; summarize recent research on the roles of tRFs in different types of cancer; and discuss the potential of using tRFs as clinical biomarkers for cancer diagnosis and prognosis and as therapeutic targets for cancer treatment. Keywords: Biomarkers, Cancer, Epigenetic regulation, RNA silencing, Translation regulation, tRNA-derived fragments
Introduction The intricate molecular mechanisms of tumorigenesis and development have always been a prime focus for cancer research. In addition to protein-coding messenger RNAs (mRNAs), research over the past few decades has elucidated roles for non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and small non-coding RNAs (sncRNAs), in various biological processes. ncRNAs’ involvement in complex mechanisms that play crucial roles in the development and progression of cancers [1–4] has been elucidated, thus challenging the previous views of these molecules as merely transcriptional “junk.” In recent years, with the development of highthroughput sequencing technology and improvements in * Correspondence: [email protected] 2 Center for Uterine Cancer Diagnosis & Therapy Research of Zhejiang Province, Women’s Reproductive Health Key Laboratory of Zhejiang Province, Department of Gynecologic Oncology, Women’s Hospital and Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China Full list of author information is available at the end of the article
bioinformatics analysis, a new class of sncRNAs derived from tRNAs has been discovered. These tRNA-derived ncRNAs are called tRNA fragments (tRFs). Far from being random tRNA degradation products [5–7], the biogenesis of tRFs is actually controlled by a set of highly conservative and precise site-specific cutting mechanisms that produce transcripts that are 14–50 nucleotides in length [8–11]. There
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