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. 2021 Jul;22(1):506.
doi: 10.3892/ol.2021.12767. Epub 2021 May 2.

Screening and potential role of tRFs and tiRNAs derived from tRNAs in the carcinogenesis and development of lung adenocarcinoma

Jinhua Zhang  1 , Linhui Li  1 , Lilin Luo  1 , Xuantao Yang  1 , Juanjuan Zhang  1 , Yuxin Xie  1 , Rui Liang  2 , Wanpu Wang  1 , Shuaiyao Lu  3
Affiliations

Screening and potential role of tRFs and tiRNAs derived from tRNAs in the carcinogenesis and development of lung adenocarcinoma

Jinhua Zhang et al. Oncol Lett. 2021 Jul.

Abstract

Accumulating evidence has indicated that a group of novel molecules, known as transfer RNA (tRNA)-derived fragments (tRFs) and tRNA halves (tiRNAs), which are derived from tRNAs, serve an essential role in numerous types of human disease, in particular solid tumors. However, to the best of our knowledge, the underlying mechanisms of the effect of tRFs and tiRNAs in lung adenocarcinoma have not been reported. The present study aimed to determine the differential expression levels of tRFs and tiRNAs in lung adenocarcinoma and adjacent tissues using a NextSeq system, and further investigated their potential target genes via bioinformatics analysis. Kyoto Encyclopedia of Genes and Genomes signaling pathway and Gene Ontology functional term enrichment analyses were performed to investigate the function of these target genes in the occurrence and development of lung adenocarcinoma. In patients with lung adenocarcinoma, 338 types of tRFs and tiRNAs were detected via sequencing, 284 of which were not previously reported in the tRF database. Compared with the adjacent tissues, 17 types of tRFs and tiRNAs comprising 34 subtypes were found to be abnormally expressed in lung adenocarcinoma tissues, 20 of which were upregulated and 14 downregulated. Reverse transcription-quantitative PCR verification revealed that the expression levels of tiRNA-Lys-CTT-002, tRF-Val-CAC-010 and tRF-Val-CAC-011 were significantly upregulated, while those of tRF-Ser-TGA-005 were downregulated in lung adenocarcinoma tissues. Bioinformatics analysis identified that tRF-Ser-TGA-005 participated in the 'cellular response to transforming growth factor β stimulus' and tRF-Val-CAC-010 and tRF-Val-CAC-011 participated in the 'Hedgehog signaling pathway'. In conclusion, the results of the present study suggested that tRFs and tiRNAs may be closely associated with the pathogenesis and development of lung adenocarcinoma, providing a novel insight for further studies into lung adenocarcinoma.

Keywords: diagnostic biomarker; lung adenocarcinoma; pathogenesis; transfer RNA halves; transfer RNA-derived fragments.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1.
Figure 1.
tRFs and tiRNAs screened from lung adenocarcinoma and adjacent tissues. (A) Venn diagram of the number of tRFs and tiRNAs known and stored in the tRF database and those detected in the present study. (B) Venn diagram based on the number of common and differentially expressed tRFs and tiRNAs in lung adenocarcinoma and adjacent tissues. tRFs, transfer RNA-derived fragments; tiRNAs, transfer RNA halves.
Figure 2.
Figure 2.
Differently expressed tRFs and tiRNAs identified between lung adenocarcinoma and adjacent tissues. (A) Heat map demonstrating the significant changes in the expression levels of tRFs and tiRNAs between lung adenocarcinoma and adjacent tissues. Red represents high expression; blue represents low expression. (B) Volcano plot showing the number of differentially expressed tRFs and tiRNAs. (C) Scatter plot representing the differentially expressed tRFs and tiRNAs in lung adenocarcinoma and adjacent tissues. (D) Reverse transcription-qPCR analysis of the top 10 differentially expressed tRFs and tiRNAs. *P<0.05. ns, not significant; tRFs, transfer RNA-derived fragments; tiRNAs, transfer RNA halves; qPCR, quantitative PCR.
Figure 3.
Figure 3.
Pie charts of the distribution of tRF and tiRNA subtypes. (A) Lung adenocarcinoma and (B) adjacent tissues. tRFs, transfer RNA-derived fragments; tiRNAs, transfer RNA halves.
Figure 4.
Figure 4.
Association and structure of differentially expressed tRFs and tiRNAs. (A) Association between tRFs and target genes. Red represents tRF and tiRNA; green represents the altered target genes. (B) Structure of tRFs and tiRNAs. Yellow represents the sequences of tRF and tiRNA. Green represents the remaining sequences of mature tRNA after cleavage. tRFs, transfer RNA-derived fragments; tiRNAs, transfer RNA halves.
Figure 5.
Figure 5.
Most significantly enriched KEGG signaling pathways of target mRNAs associated with tiRNA-Lys-CTT-002. tiRNAs, transfer RNA halves; KEGG, Kyoto Encyclopedia of Genes and Genomes.
Figure 6.
Figure 6.
Most significantly enriched KEGG signaling pathways of target mRNAs associated with tRF-Ser-TGA-005. tRFs, transfer RNA-derived fragments; KEGG, Kyoto Encyclopedia of Genes and Genomes.
Figure 7.
Figure 7.
Most significantly enriched KEGG signaling pathways of target mRNAs associated with tRF-Val-CAC-010. tRFs, transfer RNA-derived fragments; KEGG, Kyoto Encyclopedia of Genes and Genomes.
Figure 8.
Figure 8.
Most significantly enriched KEGG signaling pathways of target mRNAs associated with tRF-Val-CAC-011. tRFs, transfer RNA-derived fragments; KEGG, Kyoto Encyclopedia of Genes and Genomes.
Figure 9.
Figure 9.
Most significant GO terms of target mRNAs associated with differentially expressed tRFs and tiRNAs. (A) tiRNA-Lys-CTT-002. (B) tRF-Ser-TGA-005 (*GO:0016706: Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors). (C) tRF-Val-CAC-010. (D) tRF-Val-CAC-011. tRFs, transfer RNA-derived fragments; tiRNAs, transfer RNA halves; GO, Gene Ontology.
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