Screening and Comprehensive Analysis of Cancer-Associated tRNA-Derived Fragments.

Yiran Zhou,Yuan Zhou,Qinghua Cui

doi:10.3389/fgene.2021.747931

Abstract

tRNA-derived fragments (tRFs) constitute a novel class of small non-coding RNA cleaved from tRNAs. In recent years, researches have shown the regulatory roles of a few tRFs in cancers, illuminating a new direction for tRF-centric cancer researches. Nonetheless, more specific screening of tRFs related to oncogenesis pathways, cancer progression stages and cancer prognosis is continuously demanded to reveal the landscape of the cancer-associated tRFs. In this work, by combining the clinical information recorded in The Cancer Genome Atlas (TCGA) and the tRF expression profiles curated by MINTbase v2.0, we systematically screened 1,516 cancer-associated tRFs (ca-tRFs) across seven cancer types. The ca-tRF set collectively combined the differentially expressed tRFs between cancer samples and control samples, the tRFs significantly correlated with tumor stage and the tRFs significantly correlated with patient survival. By incorporating our previous tRF-target dataset, we found the ca-tRFs tend to target cancer-associated genes and onco-pathways like ATF6-mediated unfolded protein response, angiogenesis, cell cycle process regulation, focal adhesion, PI3K-Akt signaling pathway, cellular senescence and FoxO signaling pathway across multiple cancer types. And cell composition analysis implies that the expressions of ca-tRFs are more likely to be correlated with T-cell infiltration. We also found the ca-tRF expression pattern is informative to prognosis, suggesting plausible tRF-based cancer subtypes. Together, our systematic analysis demonstrates the potentially extensive involvements of tRFs in cancers, and provides a reasonable list of cancer-associated tRFs for further investigations.

Highlights

As its name implied, tRNA-derived fragment, is a novel class of non-coding RNA cleaved from mature transfer RNAs (Lee et al, 2009; Thompson and Parker, 2009)
Three tRNA-derived fragments (tRFs) sets, including the differentially expressed tRFs between cancer samples and normal samples, the tRFs significantly correlated with clinical tumor stage and the tRFs significantly correlated with patient survival, were firstly constructed as candidate sources of cancer-associated tRFs (ca-tRFs) (See Materials and Methods)
If one tRF is detectable in no less than 10% samples and exists in at least two sets, it was determined as a ca-tRF (Figure 2; Supplementary Data S1)

Summary

Introduction

TRNA-derived fragment (tRF), is a novel class of non-coding RNA (ncRNA) cleaved from mature transfer RNAs (tRNA) (Lee et al, 2009; Thompson and Parker, 2009). In recent years, extending scope of tRFs’ biological functions had been uncovered, bringing tRFs back to researchers’ view (Li et al, 2018). Some tRFs are found capable of facilitating ribosome biogenesis by interacting with Twi. Screening Cancer-Associated tRFs to enhance pre-rRNA processing (Couvillion et al, 2012) or accelerating the mRNA translation of ribosomal proteins (Kim et al, 2017). Some other tRFs were reported to be capable to reduce global translation efficiency (Yamasaki et al, 2009; Ivanov et al, 2011), regulate immuno-functions (Wang et al, 2006) and serve as epigenetic regulators (Chen et al, 2016)

Methods

Results

Conclusion