5′-tRNA Halves are Dysregulated in Clear Cell Renal Cell Carcinoma

Zhao, Chenming; Tolkach, Yuri; Schmidt, Doris; Kristiansen, Glen; Müller, Stefan; Ellinger, Jörg

doi:10.1016/j.juro.2017.07.082

Cited by 46 publications

(42 citation statements)

References 18 publications

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“…tsRNAs take part in cellular processes including cell proliferation (12,31), metastasis (32) and apoptosis (32,33). Diagnostic potential of tsRNAs was also reported in prostate cancer (34), liver cancer (8) and clear cell renal cell carcinoma (23). Although the function of tsRNAs remains largely unknown in cancer process, but they may be suitable as cancer biomarkers (35).…”

Section: Discussionmentioning

confidence: 99%

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Serum tRNA-derived small RNAs as potential novel diagnostic biomarkers for Pancreatic Ductal Adenocarcinoma

Xue

Shi

Xie

et al. 2020

Preprint

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Background Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal common cancer because of late diagnosis. tRNA-derived small RNAs (tsRNAs) are novel small RNAs might serve as biomarkers for cancer diagnosis and participate in diverse physiological and pathological process. We investigated whether the expression of tsRNAs in serum could be a noninvasive method in the early diagnosis of PDAC.Methods Blood sample of PDAC patients and healthy controls were collected from Ruijin Hospital, Shanghai, China. Tumor and adjacent normal pancreas tissues were collected from 51 patients with PDAC undergoing therapeutic surgery. The testing cohort comprised 6 PDAC patients and 6 healthy controls and the expression of small RNAs in serum was analyzed by small RNA sequence. We verified the diagnostic performance of serum tsRNAs by qPCR in validation cohort including 110 PDAC patients and 100 healthy controls. Expression level of tsRNAs in tissue was also verified in another independent cohort including 51 tumor and 51 adjacent normal pancreas tissues. Unpaired t-test and paired t-test are used for comparing depending on whether the samples are paired. Receiver operating characteristic (ROC) area under the curve (AUC) was used to determine diagnostic accuracy.Results There were 45 tsRNAs expressed at remarkably higher levels, 6 tsRNAs expressed at lower levels in PDAC patients, respectively, compared with healthy volunteers. tsRNA-ValTAC-41, tsRNA-MetCAT-37 and tsRNA-ThrTGT-23 expressed significant highly (P<0.05) in serum of PDAC patients in validation cohort. tsRNA-ValTAC-41 or tsRNA-MetCAT-37 combined with CA19-9 could increase the AUC of PDAC prediction (AUC=0.947 and 0.949 respectively), relative to CA19-9 test alone. Besides, tsRNA-ValTAC-41 expressed at remarkably higher level in tumor tissue, and it was obviously associated with tumor staging both in serum and tissue.Conclusions We provide tsRNAs profiles observed by small RNA sequencing. The diagnostic accuracy of tsRNA-ValTAC-41 and tsRNA-MetCAT-37 in serum of PDAC patients were verified. Further studies for tsRNA-ValTAC-41 are needed to confirm the findings. These tsRNAs may be promising and effective candidates in the development of highly sensitive, noninvasive biomarkers for PDAC diagnosis.

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Section: Discussionmentioning

confidence: 99%

“…In order to measure tsRNAs levels in each sample, tsRNAs were ampli ed selectively without full-length tRNA quanti cation by existing protocol (23,24). The serum or tissue RNA was poly-A tailed using E. coli Poly(A) Polymerase (NEB, M0276) for 30 minutes at 37 °C followed by 10 minutes at 65 °C.…”

Section: Tsrnas Quanti Cationmentioning

confidence: 99%

Serum tRNA-derived small RNAs as potential novel diagnostic biomarkers for Pancreatic Ductal Adenocarcinoma

Xue

Shi

Xie

et al. 2020

Preprint

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“…The tRNA halves have been associated with diseases ( Honda et al, 2015 ; Nientiedt et al, 2016 ; Zhao et al, 2018 ). Angiogenin is a ribonuclease that under stress conditions cleaves tRNA at the anticodon loop, producing tRNA-derived fragments, including tRNA halves ( Ivanov et al, 2011 ; Saikia et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Association of Transfer RNA Fragments in White Blood Cells With Antibody Response to Bovine Leukemia Virus in Holstein Cattle

et al. 2018

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Bovine leukemia virus (BLV) affects cattle health and productivity worldwide, causing abnormal immune function and immunosuppression. Transfer RNA fragments (tRFs) are known to be involved in inhibition of gene expression and have been associated with stress and immune response, tumor growth, and viral infection. The objective of this study was to identify tRFs associated with antibody response to BLV in Holstein cattle. Sera from 14 animals were collected to establish IgG reactivity to BLV by ELISA. Seven animals were seropositive (positive group) and seven were seronegative (negative group) for BLV exposure. Leukocytes from each animal were collected and tRFs were extracted for sequencing. tRF5GlnCTG, tRF5GlnTTG, and tRF5HisGTG, were significantly different between seropositive and seronegative groups (P < 0.0067). In all cases the positive group had a lower number of normalized sequences for tRFs when compared to the negative group. Result suggests that tRF5s could potentially be used as biomarkers to establish exposure of cattle to BLV.

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“…Therefore, it is reasonable to believe that tsRNA is a new target for tumor therapy. Besides, tsRNAs can be detected in the urine and serum from tumor patients [ 69 , 70 , 71 ], suggesting they can be used as molecular markers for tumor diagnosis. For example, Dhahbi et al found that the level of tsRNAs in the blood samples from breast cancer patients was closely related to the pathological characteristics through small RNA high-throughput sequencing analysis [ 72 ]; Honda et al found that a kind of hormone dependent tsRNA was abundant in breast cancer and prostate cancer and can enhance the proliferation of cancer cells [ 16 ].…”

Section: Roles Of Trna-derived Small Rna In Diseasesmentioning

confidence: 99%

tRNA-Derived Small RNA: A Novel Regulatory Small Non-Coding RNA

Sheng

2018

Genes

240

218

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Deep analysis of next-generation sequencing data unveils numerous small non-coding RNAs with distinct functions. Recently, fragments derived from tRNA, named as tRNA-derived small RNA (tsRNA), have attracted broad attention. There are mainly two types of tsRNAs, including tRNA-derived stress-induced RNA (tiRNA) and tRNA-derived fragment (tRF), which differ in the cleavage position of the precursor or mature tRNA transcript. Emerging evidence has shown that tsRNAs are not merely tRNA degradation debris but have been recognized to play regulatory roles in many specific physiological and pathological processes. In this review, we summarize the biogeneses of various tsRNAs, present the emerging concepts regarding functions and mechanisms of action of tsRNAs, highlight the potential application of tsRNAs in human diseases, and put forward the current problems and future research directions.

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5′-tRNA Halves are Dysregulated in Clear Cell Renal Cell Carcinoma

Abstract: In patients with clear cell renal cell carcinoma 5'-tRNA halves have potential as diagnostic and prognostic biomarkers. The 5'-tRNA halves may act in a tumor suppressive manner, which requires further research to confirm.

Cited by 46 publications

References 18 publications

Serum tRNA-derived small RNAs as potential novel diagnostic biomarkers for Pancreatic Ductal Adenocarcinoma

Serum tRNA-derived small RNAs as potential novel diagnostic biomarkers for Pancreatic Ductal Adenocarcinoma

Association of Transfer RNA Fragments in White Blood Cells With Antibody Response to Bovine Leukemia Virus in Holstein Cattle

tRNA-Derived Small RNA: A Novel Regulatory Small Non-Coding RNA

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