Genome-wide identification and characterization of aberrant tRNA-derived RNA fragments in non-small cell lung cancer.

e20539 Background: tRNA-derived RNA fragments (tRFs) represent a new class of non-coding single-stranded RNAs with 14-35 nt in length. Recent studies suggest that tRFs play important roles in cellular processes and are involved in multiple cancers. However, rather little is known about the role of tRFs in non-small cell lung cancer (NSCLC), one of the most common cancers worldwide. Methods: We used RNA-sequencing to compare the expression profiles of tRFs in 10 pairs of pre- and post-operation plasma samples from patients with NSCLC. We validated the expression of differentially expressed (DE-) tRFs using qPCR. We further investigated the biological functions of DE-tRFs in three NSCLC cell lines (A549, NCI-1650, and NCI-226). Results: We detected 6660 unique tRFs, among them tRF-5 is the most abundant class of tRFs, followed by tRF-3 class. We identified 8 DE-tRFs that were differentially expressed (DE-) between pre- and post-operation plasma samples (fold change ≥1.5, P<0.05). We found that these DE-tRFs contained seed sequences targeting genes enriched in cancer-related pathways such as Wnt signaling and carbon metabolism. Transfection of AS-tDR-007333 and AS-tDR-010968, two up-regulated tRFs in pre-operation plasma samples, into NSCLC cell lines promoted proliferation, migration, and apoptosis. While knockdown of AS-tDR-007333 and AS-tDR-010968 suppressed cell proliferation, migration, and apoptosis. Conclusions: Our study provides a systematic catalogue of circulating tRFs and their dysregulation in NSCLC that can serve as the basis for further research on the roles of tRFs in diagnostic biomarker and therapeutic target in NSCLC.