Global Identification and Characterization of TRNA-derived RNA Fragment Landscapes Across Human Cancers

Overview

Journal NAR Cancer

Publisher Oxford University Press

Specialty Oncology

Date 2021 Jul 28

PMID 34316691

Citations 15

Authors

Xiwei Sun

Juze Yang

Mengqian Yu

Dongxia Yao

Liyuan Zhou

Xufan Li

Qiongzi Qiu

Weiqiang Lin

Bingjian Lu

Enguo Chen

Ping Wang

Wantao Chen

Sifeng Tao

Haiming Xu

Anna Williams

Yong Liu

Xiaoqing Pan

Allen W Cowley Jr

Weiguo Lu

Mingyu Liang

Pengyuan Liu

Yan Lu

Affiliations

Soon will be listed here.

Abstract

Transfer RNA-derived RNA fragments (tRFs) are a class of small non-coding RNAs that are abundant in many organisms, but their role in cancer has not been fully explored. Here, we report a functional genomic landscape of tRFs in 8118 specimens across 15 cancer types from The Cancer Genome Atlas. These tRFs exhibited characteristics of widespread expression, high sequence conservation, cytoplasmic localization, specific patterns of tRNA cleavage and conserved cleavage in tissues. A cross-tumor analysis revealed significant commonality among tRF expression subtypes from distinct tissues of origins, characterized by upregulation of a group of tRFs with similar size and activation of cancer-associated signaling. One of the largest superclusters was composed of 22 nt 3'-tRFs upregulated in 13 cancer types, all of which share the activation of Ras/MAPK, RTK and TSC/mTOR signaling. tRF-based subgrouping provided clinically relevant stratifications and significantly improved outcome prediction by incorporating clinical variables. Additionally, we discovered 11 cancer driver tRFs using an effective approach for accurately exploring cross-tumor and platform trends. As a proof of concept, we performed comprehensive functional assays on a non-microRNA driver tRF, 5'-IleAAT-8-1-L20, and validated its oncogenic roles in lung cancer and . Our study also provides a valuable tRF resource for identifying diagnostic and prognostic biomarkers, developing cancer therapy and studying cancer pathogenesis.

Citing Articles

Research progress on the tsRNA biogenesis, function, and application in lung cancer.

Chen Y, Shao Z, Wu S Noncoding RNA Res. 2024; 10:63-69.

PMID: 39309197 PMC: 11414277. DOI: 10.1016/j.ncrna.2024.09.004.

Expression profiles of serum transfer RNA-derived fragments and their potential roles in non-small cell lung cancer.

Song Y, Li J Transl Cancer Res. 2024; 13(7):3668-3677.

PMID: 39145073 PMC: 11322679. DOI: 10.21037/tcr-23-2364.

tRNA-derived fragments: mechanism of gene regulation and clinical application in lung cancer.

Wu F, Yang Q, Pan W, Meng W, Ma Z, Wang W Cell Oncol (Dordr). 2023; 47(1):37-54.

PMID: 37642916 DOI: 10.1007/s13402-023-00864-z.

NGS Data Repurposing Allows Detection of tRNA Fragments as Gastric Cancer Biomarkers in Patient-Derived Extracellular Vesicles.

Maqueda J, Santos M, Ferreira M, Marinho S, Rocha S, Rocha M Int J Mol Sci. 2023; 24(10).

PMID: 37240307 PMC: 10219402. DOI: 10.3390/ijms24108961.

Characterization of tRNA-Derived Fragments in Lung Squamous Cell Carcinoma with Respect to Tobacco Smoke.

Magesh S, Gande P, Yalamarty R, John D, Chakladar J, Li W Int J Mol Sci. 2023; 24(6).

PMID: 36982573 PMC: 10057801. DOI: 10.3390/ijms24065501.

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