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

Mol Biol Rep. 2021 Nov;48(11):7313-7324. doi: 10.1007/s11033-021-06732-z. Epub 2021 Oct 18.

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.

Keywords: Breast cancer; miRNA; tRNA derived fragments.

MeSH terms

  • Adult
  • Biomarkers, Tumor / blood
  • Breast Neoplasms / blood
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA, Small Untranslated / blood
  • RNA, Small Untranslated / genetics

Substances

  • Biomarkers, Tumor
  • MIRN1260 microRNA, human
  • MIRN4521 microRNA, human
  • MicroRNAs
  • RNA, Small Untranslated