Mechanisms of tRNA-derived fragments and tRNA halves in cancer treatment resistance
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REVIEW
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Mechanisms of tRNA-derived fragments and tRNA halves in cancer treatment resistance Yue Zhang†, Huizhu Qian†, Jing He* and Wen Gao*
Abstract The tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) are newly discovered noncoding RNAs in recent years. They are derived from specific cleavage of mature and pre-tRNAs and expressed in various cancers. They enhance cell proliferation and metastasis or inhibit cancer progression. Many studies have investigated their roles in the diagnosis, progression, metastasis, and prognosis of various cancers, but the mechanisms through which they are involved in resistance to cancer treatment are unclear. This review outlines the classification of tRFs and tiRNAs and their mechanisms in cancer drug resistance, thus providing new ideas for cancer treatment. Keywords: tRNA-derived fragments, tRNA halves, Cancer, Drug resistance, Biomarker
Background Transfer RNAs (tRNAs) have long been regarded as classic noncoding RNAs and are involved in protein translation [1]. Recently, many researchers have discovered new noncoding RNAs that are derived from specific cleavage of pre- and mature tRNA. Noncoding RNAs derived from tRNA are grouped into two categories: tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) [1]. The tRFs originate from mature or pre-tRNAs, and they are approximately 14–30 nucleotides (nt) in length. tiRNAs are 29–50 nt in length and originate from specific cleavage of mature tRNA anticodon loop under stress [2, 3]. The tRFs are conservative and widespread in nature [4]. They were initially discovered as random tRNA degradation fragments and later found to be generated by conservative and specific tRNA cleavage [5]. The tRFs are associated with cancer, inherited metabolic diseases, viral infections, and neurodegenerative diseases [6]. Here, we introduce the classification of tRFs and * Correspondence: [email protected]; [email protected] † Yue Zhang and Huizhu Qian contributed equally to this work. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China
tiRNAs, discuss their roles in cancers, summarize their mechanisms of drug resistance in cancer treatment, and describe techniques for studying tRFs and tiRNAs. Classification of tRFs and tiRNAs and their roles in cancers
The tRFs include tRF-1, tRF-2, tRF-3, tRF-5, and i-tRF [5] (Fig. 1). The tRF-1 is produced by cleaving 3′ pretRNA by RNase Z or its cytoplasmic ribonuclease Z 2 (ELAC2) in the TψC loop [7]. tRF-1 has carcinogenic or anticancer effects in the occurrence and development of cancers [5]. tRF-2 is derived from the decomposition of anticodon loops of tRNAs under hypoxic condition [8]. Angiogenin and Dicer cleave the T-loop of 3′-ends of mature tRNA to produce tRF-3. tRF-3 includes tRF-3a and tRF-3b [7, 8]. Dicer cleaves the D-loop of tRNA to produce tRF-5. tRF-5 includes tRF-5a, tRF-5b, and tRF5c [5]. The tRF-5 is mostly located in the nucleus, whereas tRF-3 and tRF-1 mainly occur in the cytoplasm [8]. The i-tRF
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