4.6 Article

Identification of MicroRNAs as Breast Cancer Prognosis Markers through the Cancer Genome Atlas

Journal

PLOS ONE
Volume 11, Issue 12, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0168284

Keywords

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Funding

  1. National Institutes of Health/NIDDK [2T35DK062719-26]
  2. National Institute of Health [K08GM089941, R21 CA139278, UO1GM61393]
  3. University of Chicago Support Grant [P30 CA14599]
  4. Breast Cancer SPORE Career Development Award [CA125183]
  5. National Center for Advancing Translational Sciences of the National Institute of Health [UL1RR024999]
  6. Circle of Service Foundation Early Career Investigator award
  7. Avon Foundation Research Grant
  8. Conquer Cancer Foundation of ASCO Translational Research Professorship award

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Breast cancer is the second-most common cancer and second-leading cause of cancer mortality in American women. The dysregulation of microRNAs ( miRNAs) plays a key role in almost all cancers, including breast cancer. We comprehensively analyzed miRNA expression, global gene expression, and patient survival from the Cancer Genomes Atlas (TCGA) to identify clinically relevant miRNAs and their potential gene targets in breast tumors. In our analysis, we found that increased expression of 12 mature miRNAs D hsa-miR-320a, hsami-R-361-5p, hsa-miR-103a-3p, hsa-miR-21-5p, hsa-miR-374b-5p, hsa-miR-140-3p, hsami-R-25-3p, hsa-miR-651-5p, hsa-miR-200c-3p, hsa-miR-30a-5p, hsa-miR-30c-5p, and hsa-let-7i-5p D each predicted improved breast cancer survival. Of the 12 miRNAs, miR320a, miR-361-5p, miR-21-5p, miR-103a-3p were selected for further analysis. By correlating global gene expression with miRNA expression and then employing miRNA target prediction analysis, we suggest that the four miRNAs may exert protective phenotypes by targeting breast oncogenes that contribute to patient survival. We propose that miR-320a targets the survival-associated genes RAD51, RRP1B, and TDG; miR-361-5p targets ARCN1; and miR-21-5p targets MSH2, RMND5A, STAG2, and UBE2D3. The results of our stringent bioinformatics approach for identifying clinically relevant miRNAs and their targets indicate that miR-320a, miR-361-5p, and miR-21-5p may contribute to breast cancer survival.

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