A tRNA fragment, 5′-tiRNAVal, suppresses the Wnt/β-catenin signaling pathway by targeting FZD3 in breast cancer

Mo, Dongping; Jiang, Pan; Yang, Yining; Mao, Xuelian; Tan, Xiaojie; Tang, Xun; Da, Wang; Li, Bing; Wang, Xiaoming; Tang, Li; Yan, Feng

doi:10.1016/j.canlet.2019.05.007

Cited by 106 publications

(128 citation statements)

References 46 publications

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“…Third, the hg38 sequence information of tRFs is not updated in public databases. Additionally, tiRNAs and tRFs not included in tRFdb, such as 5'-tiRNAVal and tRF5-Glu, which have been reported to repress mRNA by seed pairing (18,43,44), were not considered in this version.…”

Section: Discussionmentioning

confidence: 99%

tRFTar: predicting the targets of tRNA-derived fragments

Xiao

Gao

Huang

et al. 2020

Preprint

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Background: tRNA-derived fragments (tRFs) are 14–40-nucleotide-long, small non-coding RNAs derived from specific tRNA cleavage events with key regulatory functions in many biological processes. Many studies have shown that tRFs are associated with Argonaute (AGO) complexes and inhibit gene expression in the same manner as miRNAs. However, there are currently no tools for accurately predicting tRF target genes. Methods: We used tRF-mRNA pairs identified by crosslinking, ligation, and sequencing of hybrids (CLASH) and covalent ligation of endogenous AGO-bound RNAs (CLEAR)-CLIP to assess features that may participate in tRF targeting, including the sequence context of each site and tRF-mRNA interactions. We applied genetic algorithm (GA) to select key features and support vector machine (SVM) to construct tRF prediction models. Results: We first identified features that globally influenced tRF targeting. Among these features, the most significant were the minimum free folding energy (MFE), position 8 match, number of bases paired in the tRF-mRNA duplex, and length of the tRF, which were consistent with previous findings. Our constructed model yielded an area under the receiver operating characteristic (ROC) curve (AUC) = 0.980 (0.977-0.983) in the training process and an AUC = 0.847 (0.83-0.861) in the test process. The model was applied to all the sites with perfect Watson-Crick complementarity to the seed in the 3' untranslated region (3'-UTR) of the human genome. Seven of nine target/nontarget genes of tRFs confirmed by reporter assay were predicted. Conclusions: Predictions can be obtained online, tRFTar, freely available at http://trftar.cmuzhenninglab.org:3838/tar/, which is the first tool to predict targets of tRFs in humans with a user-friendly interface.

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Section: Discussionmentioning

confidence: 99%

tRFTar: predicting the targets of tRNA-derived fragments

Xiao

Gao

Huang

et al. 2020

Preprint

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“…In summary, tRFs and tiRNAs have important roles in gene expression, gene translation, and the development and progression of various DT tumors (17). They affect tumor cell proliferation, migration and invasion (48,57). To date, the origin and function of tRFs and tiRNAs remain to be fully elucidated, and their roles in DT tumor progression also require further investigation.…”

Section: Summary and Future Directionsmentioning

confidence: 99%

The role of Transfer RNA-Derived Small RNAs (tsRNAs) in Digestive System Tumors

Wang¹,

Yan²,

Xu³

et al. 2020

J. Cancer

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Transfer RNA-derived small RNA(tsRNA) is a type of non-coding tRNA undergoing cleavage by specific nucleases such as Dicer. TsRNAs comprise of tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs). Based on the splicing site within the tRNA, tRFs can be classified into tRF-1, tRF-2, tRF-3, tRF-5, and i-tRF. TiRNAs can be classified into 5′-tiRNA and 3′-tiRNA. Both tRFs and tiRNAs have important roles in carcinogenesis, especially cancer of digestive system. TRFs and tiRNAs can promote cell proliferation and cell cycle progression by regulating the expression of oncogenes, combining with RNA binding proteins such as Y-box binding protein 1 (YBX1) to prevent transcription. Despite many reviews on the basic biological function of tRFs and tiRNAs, few have described their correlation with tumors especially gastrointestinal tumor. This review focused on the relationship of tRFs and tiRNAs with the biological behavior, clinicopathological characteristics, diagnosis, treatment and prognosis of digestive system tumors, and would provide novel insights for the early detection and treatment of digestive system tumors.

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“…Additionally, 5'-tiRNA-Val by inhibition of FZD3/Wnt/β-Catenin signaling pathway served as diagnostic markers. TRNA-Val and tRNA-Asp were the most prevalent as well as lower levels of tRNA-Val-CAC (AS-tDR-001430) in tumor tissues and serum of the patients with higher TNM stages and lymph node metastasis and inhibition progression [42]. tsRNA-26576 upregulation induced migration while suppressing the cellular apoptosis, and served as a potential target therapy and also a predictive marker [43].…”

Section: Breast Cancermentioning

confidence: 99%

Dynamic Signature of tRNA-Derived Small RNAs in Cancer Pathogenesis as a Promising Valuable Approach

Vafaei

Fattahi

Sahlolbei

et al. 2020

Crit Rev Eukaryot Gene Expr

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Background: Non-coding RNAs are a cluster of RNAs that do not encode functional proteins, and involve infrastructural and regulatory types, which transfer RNAs (tRNAs) belong to former and small RNAs (sRNA) to the latter one. Recently, tRNA-derived small RNAs (tDRs) were discovered among small non-coding RNA, as the newly discovered regulatory small RNA. It plays a role in pathological and physiological processes, which is frequently dysregulated in gene expression regulation. tsRNAs can be bounded to argonaute proteins and piwi proteins such as miRNAs and piRNAs sequentially. In addition, it can interact with DNA and histone methylation machinery Results: In initial searching, 2744 unique articles were identified by bio electronically search of following databases: PubMed, Embase, Web of Science, Scopus, and google scholar up to 25 February 2020. Finally, after Full-text assessment 48 related article to gene expression profiling tsRNA in cancer were achieved. Conclusions: In this systematic review, we summarized the most recent findings related to the expression of tsRNAs in 17 cancer types. We suggested that tsRNA in cancer field attracted the researchers' focus and effectively facilitated diagnostic and therapy approaches. There is little consensus over tRF production mechanism, and dicer-dependent cleavage of mature tRNAs has been suggested [11]. Dysregulation of tsRNAs could interfere in the gene expression in pre/post transcriptional and protein translation. Furthermore, researchers target the tsRNA via gene repression of mRNAs, reported construct silencing, translation inhibition, cell proliferation modulation, exonuclease mRNAs Xrn2-mediated degradation, Ybx1 protein displacement, and sense-induced trans-silencing [12]. Moreover, they have been engaged in cellular and pathophysiological tools, concerning porphyrin biosynthesis, reverse transcription, cell proliferation, differentiation, viability, cell signalling, control of viral replication, and utterly in disease ranging from metabolic disorders and neuro degenerative disease to various types of cancer [13-19]. At first, in 2009, small RNA sequencing data was recognized as tsRNA in prostate cancer [20]. Then, the scientists analyzed more samples, which were abundant in small RNA [21]. They declared that, this biomarker could be potentially applied in many cancer types as a screening and even be targeted for therapy. Moreover, tsRNA is essential in cell cycle proliferation and propagation as well as playing a significant role in tumorigenesis either oncogenic or tumor-suppressor functions [22]. Besides, induction and dysregulation of a set of hypoxia related tsRNAs and also tsRNA suppressive factors in Notch signaling pathway can help in maintenance and metastasis of cancer stem cell [23, 24]. Unfortunately, the exact pathway of tsRNA in cancer has not been clarified yet and we design the schematic of tRNA-derived small RNAs biogenesis in Fig. 1. In this systematic review, we summarized the frequency and function of tsRNAs in different cancer types. Met...

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A tRNA fragment, 5′-tiRNAVal, suppresses the Wnt/β-catenin signaling pathway by targeting FZD3 in breast cancer

Cited by 106 publications

References 46 publications

tRFTar: predicting the targets of tRNA-derived fragments

tRFTar: predicting the targets of tRNA-derived fragments

The role of Transfer RNA-Derived Small RNAs (tsRNAs) in Digestive System Tumors

Dynamic Signature of tRNA-Derived Small RNAs in Cancer Pathogenesis as a Promising Valuable Approach

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