5′-tRF-GlyGCC promotes breast cancer metastasis by increasing fat mass and obesity-associated protein demethylase activity

Chen, Fang; Song, Chengchuang; Meng, Fantong; Zhu, Yuhua; Chen, Xi; Fang, Xingtang; Ma, Daifu; Wang, Yanhong; Zhang, Chunlei

doi:10.1016/j.ijbiomac.2022.11.295

Cited by 13 publications

(10 citation statements)

References 57 publications

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“…Quantitative PCR further veri ed that tRF3a-GlyGCC-1 were signi cantly up-regulated only in WAT of mice fed with high-fat VD de ciency diet compared with low-fat VD su ciency diet. Several studies showed that 5'-tRF-GlyGCC promoted breast tumorigenesis and metastasis (33), and was correlated with an aggressive phenotype of ovarian tumor (34), and was a novel biomarker for colorectal cancer diagnosis (35). our study found that tRF3a-GlyGCC-1 were greatly in uenced by both circulating VD concerntrtion and degree of fatness.…”

Section: Discussionsupporting

confidence: 55%

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

Jia,

Zhao

2023

Preprint

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Background The expression of tsRNA in white adipose tissue (WAT) of VD deficiency male mice with obesity has not been reported. Methods The healthy male C57BL/6J mice aged 4–6 weeks were divided into 4 groups according to the VD3 and fat energy supplement in daily diets. Results The qPCR verification further demonstrated that 1 tsRNAs (tRF5-20-HisGTG-3, all P < 0.05) were significantly up-regulated and 1 tsRNA (mt-tRF3a-ProTGG, all P < 0.05) was significantly down-regulated not only in HFVDD vs HFVDS, but aslo in HFVDD vs ConVDS. 1 tsRNAs (tRF5-22-CysGCA-27, P < 0.05) were significantly up-regulated and 3 tsRNA (mt-5'tiRNA-32-SerTGA, mt-5'tiRNA-33-SerTGA and mt-5'tiRNA-33-AlaTGC, all P < 0.05) was significantly down-regulated only in HFVDD vs ConVDS. Enrichment analysis of the qPCR verified DE tsRNAs showed that the 3 up-regulated tsRNAs seemed to be associated with FoxO signaling pathway, GnRH secretion, 2 − Oxocarboxylic acid metabolism, Autophagy – animal, Glucagon signaling pathway, AGE − RAGE signaling pathway in diabetic complications, Insulin signaling pathway, Apelin signaling pathway, Alzheimer disease, Pathways of neurodegeneration − multiple diseases, while 4 down-regulated tsRNA seemed to be associated with cell communication, primary metabolic process, metabolic process, response to stimulus, multicellular organismal process, cellular metabolic process, regulation of cellular process, regulation of biological process, and biological regulation. Conclusions The tsRNAs were differentially expressed in VD deficiency with obesity, especially tRF5-20-HisGTG-3, tRF5-22-CysGCA-27, tRF3a-GlyGCC-1, mt-5'tiRNA-33-AlaTGC, mt-5'tiRNA-33-SerTGA, mt-5'tiRNA-32-SerTGA and mt-tRF3a-ProTGG. These tsRNAs seemed to be associated with FoxO signaling pathway, GnRH secretion, 2 − oxocarboxylic acid metabolism, autophagy, glucagon and insulin signaling pathway, pathways of neurodegeneration − multiple diseases, metabolic process and biological regulation.

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Section: Discussionsupporting

confidence: 55%

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

Jia,

Zhao

2023

Preprint

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“…These results suggest that tRFs have miRNA-like functions in Drosophila . Although Ago-loaded tRFs were identified, they may represent only a subset of the overall expressed tsRNAs because tsRNAs have other mechanisms in addition to miRNA-like patterns, such as acting on functional proteins [ 29 ] and transcription factors [ 30 ]. In our study, a comprehensive and systematic study of tsRNAs in 7-day- and 42-day-old Drosophila was performed.…”

Section: Discussionmentioning

confidence: 99%

The Expression Pattern of tRNA-Derived Small RNAs in Adult Drosophila and the Function of tRF-Trp-CCA-014-H3C4 Network Analysis

Yang

Xiao

Yuán

et al. 2023

IJMS

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tRNA-derived small RNAs (tsRNAs) are derived from tRNA and include tRNA halves (tiRNAs) and tRNA fragments (tRFs). tsRNAs have been implicated in a variety of important biological functions, such as cell growth, transcriptional regulation, and apoptosis. Emerging evidence has shown that Ago1-guided and Ago2-guided tsRNAs are expressed at 3 and 30 days in Drosophila and that tRF biogenesis in fruit flies affects tRNA processing and tRNA methylation. However, a wide analysis of tsRNA patterns in different ages of Drosophila have not been reported via the small RNA sequencing method. In the present study, tsRNAs of young (7 days) and old (42 days) Drosophila were sequenced and their expression characteristics were analysed. Then, a specific tRF (named tRF-Trp-CCA-014) was determined and was found to be conserved in fruit flies, mice, and humans. The expression patterns of tRF-Trp-CCA-014 in different tissues and stages of fruit flies and mice, and mouse NIH/3T3 cells were detected. Furthermore, mouse embryonic fibroblast NIH/3T3 cells were used as a model to analyse the function and targets of tRF-Trp-CCA-014. The RNA-seq data of six groups (Mimics, Mimic NC, Inhibitors, Inhibitor NC, Aging (adriamycin), and Control (Normal)) in mouse NIH3T3 cells were analysed. The results showed that the number of tsRNAs at 42 days (417) was more than at 7 days (288); thus, it was enriched with age. tRFs-1 were the most enriched, followed by 5′-tRFs and 3′-tRFs. Twenty-one differentially expressed tsRNAs were identified between 7 days and 42 days. Then, the conserved tRF tRF-Trp-CCA-014 was identified and found to accumulate in aged fruit flies and aged mouse NIH3T3 cells. RNA-seq data showed that most differentially expressed genes were involved in the immune system, cancer: overview, and signal translation. Furthermore, tRF-Trp-CCA-014 was found to bind to the 3′UTR of H3C4 in a dual-luciferase reporter gene assay. tRF-Trp-CCA-014 and H3C4 were detected in the cytoplasm of aged NIH3T3 cells by RNA in situ hybridization. These results suggest that the H3C4 gene is the target of tRF-Trp-CCA-014. This study will advance the current understanding of tRF roles and their implication in Drosophila and mouse studies.

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“…One on hand, FTO promotes breast cancer cell proliferation, colony formation, cellular invasion, and metastasis in vitro and in vivo. 84…”

Section: M6a Erasers: Fto and Alkbh5mentioning

confidence: 99%

“…The role of FTO in breast cancer is complex and contradictory. One on hand, FTO promotes breast cancer cell proliferation, colony formation, cellular invasion, and metastasis in vitro and in vivo 84–86 . FTO demethylates BNIP3 mRNA and induces its degradation to inhibit apoptosis while increasing cell proliferation 85 .…”

Section: The Complex Role Of M6a Regulators As Oncoproteins and Tumou...mentioning

confidence: 99%

Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy

Guan,

Wong

2024

Cancer Medicine

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The N6‐methyladenosine (m6A) RNA modification has gained significant prominence as a new layer of regulatory mechanism that governs gene expression. Over the past decade, various m6A regulators responsible for introducing, eliminating, and recognising RNA methylation have been identified. Notably, these m6A regulators often exhibit altered expression patterns in cancer, occasionally offering prognostic value. Nonetheless, the complex roles of these regulators in human cancer pathology remain enigmatic, with conflicting outcomes reported in different studies.In recent years, a multitude of inhibitors and activators targeting m6A regulators have been reported. Several of these compounds have demonstrated promising efficacy in both in vitro and in vivo cancer models. These findings collectively underscore the dynamic landscape of m6A regulation in cancer biology, revealing its potential as a therapeutic target and prognostic indicator.

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5′-tRF-GlyGCC promotes breast cancer metastasis by increasing fat mass and obesity-associated protein demethylase activity

Cited by 13 publications

References 57 publications

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

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

The Expression Pattern of tRNA-Derived Small RNAs in Adult Drosophila and the Function of tRF-Trp-CCA-014-H3C4 Network Analysis

Targeting RNA modifications with pharmacological agents: New frontiers in cancer therapy

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