Comparative expression analysis of tRF-3001a and tRF-1003 with corresponding miRNAs (miR-1260a and miR-4521) and their network analysis with breast cancer biomarkers.

ABSTRACT

BACKGROUND: MicroRNAs and tRFs (tRNA-derived fragments) are small non-coding RNAs that are promising breast cancer (BC) biomarkers. miRNA sequences are found within tRFs. For example, miR-1260a and miR-4521 sequences are found within tRF-3001a and tRF-1003, respectively. No study has addressed the biomarker potential of these tRF-miRNA pairs in BC or their association with other BC miRNA biomarkers. METHODS AND RESULTS: Real-time PCR was performed to examine the expression of miR-1260a-tRF-3001a and miR-4521-tRF-1003 pairs in plasma of BC patients. miR-4521 and miR-1260a showed no change in plasma of breast cancer patients (n = 19). On the contrary, both the corresponding tRFs (tRF-1003 and tRF-3001a) were down-regulated. Also, we performed miRNA/mRNA network analysis for miR-1260a and miR-4521 with top degree BC biomarkers miR-16-5p and miR-93-5p. We found that they shared nine target genes. Moreover, miR-16-5p was down-regulated, and miR-93-5p was up-regulated in the same sample set. Survival analysis plotted using clinical data from Kaplan-Meier Plotter showed that all four miRNAs and 8/9 target gene expressions could predict the survival of BC patients. CONCLUSIONS: Our cohort analyses suggest that tRF-3001a and tRF-1003 serve as better biomarkers than their miRNA counterparts in addition to miR-93-5p and miR-16-5p. Also, they form a significant miRNA/mRNA biomarker cluster.