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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

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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.

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Abbreviations

tRFs:

tRNA-derived fragments

BC:

Breast cancer

tiRNA:

tRNA-derived stress-induced RNA

AGO:

Argonaute

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Acknowledgements

TV acknowledges Grants from Nitte (Deemed to be University) (NURG/STF/06/7-2015), DST-SERB (YSS/2014/000061), and DBT (BT/PR23887/MED/30/1871/2017). PSS thanks faculty seed research grant of National Institute of Technology, Calicut and DBT (BT/PR16307/MED/30/1729/2016). SAH and DKV acknowledge CSIR and DST for the fellowship. Work was initiated at Nitte (Deemed to be University), where TV was working and carried out at the Central University of Kerala. We thank Ms. Farsana M for her technical support.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Biological Sciences, Central University of Kerala, Periye, Kasargod, Kerala, 671316, India

    Shaharbhanu A. Hussain, Kunhi Valappil Deepak & Thejaswini Venkatesh

  2. Division of Molecular Genetics and Cancer, Nitte University Centre for Science Education and Research (NUCSER), NITTE (Deemed to be University), Deralakate, Mangaluru, 575018, India

    Dechamma Pandyanda Nanjappa

  3. Department of Oncosurgery, A.J. Hospital and Research Centre, Mangalore, Karnataka, 575004, India

    Viswanath Sherigar

  4. Department of Obstetrics and Gynaecology, KS Hegde Medical Academy, Mangalore, Karnataka, 575018, India

    Neetha Nandan

  5. School of Biotechnology, National Institute of Technology Calicut, Calicut, Kerala, 673601, India

    Padmanaban S. Suresh

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Contributions

TV, PSS designed the project. SAH, DKV, DPN conducted the experiments. VS and NN facilitated the procurement of clinical samples. TV, SAH, DKV, DPN performed data analysis. TV wrote the manuscript with the help of PSS, SAH, VS, and NN.

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Correspondence to Thejaswini Venkatesh.

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This research followed the tenets of the Declaration of Helsinki. The present study was initiated at Nitte University Centre for Science Education & Research (NUCSER) Mangalore, where TV was working, and further carried out at the Central University of Kerala (CUK) Kasaragod. The research protocol outlining the methodology, study subjects, sample size, data collection, and all related ethical considerations were reviewed. Ethical approval was granted by the Institutional Ethics Committee of NUCSER (February 2016; INST.EC/2015-16/002) and Institutional Human Ethics Committee of CUK (July 2017; CUK/IHEC/2017-002).

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Hussain, S.A., Deepak, K.V., Nanjappa, D.P. et al. 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 48, 7313–7324 (2021). https://doi.org/10.1007/s11033-021-06732-z

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