MicroRNA-661 upregulation in myelodysplastic syndromes induces apoptosis through p53 activation and associates with decreased overall survival

Leuk Lymphoma. 2019 Nov;60(11):2779-2786. doi: 10.1080/10428194.2019.1608528. Epub 2019 May 6.

Abstract

MicroRNA (miRNA) dysregulation contributes to myelodysplastic syndromes (MDS), and apoptosis is one of the pathogenic features of MDS. We investigated the dysregulation of miRNA expression and its biological significance in MDS. We compared the expression profiles of miRNAs encoded by chromosome 8 in 65 patients with MDS and 11 controls, and analyzed the in vitro effect of the upregulated miRNA expression. We found that compared to the controls, miR-661 was upregulated by 5.28-fold in patients with MDS. Patients with high miR-661 expression showed significantly decreased overall survival. In vitro study results demonstrated that transfection with a miR-661 mimic induced apoptosis through the activation of p53. These findings suggest that high miR-661 expression can be associated with decreased overall survival and recapitulates apoptosis, the characteristic feature of MDS.

Keywords: MDS; apoptosis; dysregulation; microRNA; pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Myelodysplastic Syndromes / genetics
  • Myelodysplastic Syndromes / metabolism
  • Myelodysplastic Syndromes / mortality*
  • Myelodysplastic Syndromes / pathology
  • Prognosis
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism*
  • Young Adult

Substances

  • Biomarkers, Tumor
  • MIRN661 microRNA, human
  • MicroRNAs
  • TP53 protein, human
  • Tumor Suppressor Protein p53