Transfer RNA-derived small RNAs in tumor microenvironment

Abstract

Transfer RNAs (tRNAs) are a class of non-coding RNAs responsible for amino acid translocation during protein synthesis and are ubiquitously found in organisms. With certain modifications and under specific conditions, tRNAs can be sheared and fragmented into small non-coding RNAs, also known as tRNA-derived small RNAs (tDRs). With the development of high-throughput sequencing technologies and bioinformatic strategies, more and more tDRs have been identified and their functions in organisms have been characterized. tRNA and it derived tDRs, have been shown to be essential not only for transcription and translation, but also for regulating cell proliferation, apoptosis, metastasis, and immunity. Aberrant expression of tDRs is associated with a wide range of human diseases, especially with tumorigenesis and tumor progression. The tumor microenvironment (TME) is a complex ecosystem consisting of various cellular and cell-free components that are mutually compatible with the tumor. It has been shown that tDRs regulate the TME by regulating cancer stem cells, immunity, energy metabolism, epithelial mesenchymal transition, and extracellular matrix remodeling, playing a pro-tumor or tumor suppressor role. In this review, the biogenesis, classification, and function of tDRs, as well as their effects on the TME and the clinical application prospects will be summarized and discussed based on up to date available knowledge.

Diagnostic and prognostic values of tsRNAs in lung cancer: A meta-analysis

“…In terms of clinical application prospects, tsRNAs can serve as living markers for early tumor diagnosis and disease monitoring owing to their spatiotemporal and tissue speci cities. Furthermore, they can aid in the precision treatment of tumors (9,10,33). Numerous studies have reported differential expression of tsRNAs in LC patients, with some tsRNAs showing potential for early diagnosis and prognosis of LC.…”

Expression profile of tsRNAs in white adipose tissue of vitamin D deficiency young male mice with or without obesity

“…In recent years, the research on tsRNA and disease disorders has gradually become a hot topic, mainly focusing on tumor diseases such as gastric cancer, lung cancer and hepatocellular carcinoma, neurodegenerative disorders and so on (23,24). However, there are no reports on the characteristics and changing patterns of tsRNA expression in WAT of VD de ciency young male mice with or without obesity, beside, the role and mechanism are not clear.…”

tRNA-derived small RNAs in human cancers: roles, mechanisms, and clinical application

“…These fragments are categorized into distinct types: tRF-1, tRF-3, tRF-5, tRF-2, and i-tRF, based on their specific sites of origin within these molecules [ 56 ]. Among them, tRF-1 (14–30 nt) is generated by RNase Z/ELAC2 catalyzing the cleavage of the 3’ end of pre-tRNAs and has a poly U characteristic, thus also known as 3’UtRF [ 57 ]. tRF-3 is produced by Dicer and ANG cleaving the TψC loop of mature tRNAs and can be further stratified into tRF-3a (18 nt) and tRF-3b (22 nt) based on its length [ 32 ].…”

“…Although the potential mechanisms regulating the biogenesis of tRFs remain unclear, increasing evidence suggests that tRNA modifications, such as 5-methylcytosine (m5C), N7-methylguanosine (m7G), and pseudouridine (Ψ), play significant roles in tRNA cleavage and fragment generation [ 57 ]. On one hand, tRNA modifications can increase the stability of tRNA structure, protecting them from being cleaved by nucleases to produce tsRNAs.…”