MicroRNA-92a-3p overexpression in peripheral blood mononuclear cells is an independent predictor of prolonged overall survival of patients with chronic lymphocytic leukemia

Leuk Lymphoma. 2019 Mar;60(3):658-667. doi: 10.1080/10428194.2018.1461861. Epub 2018 Jun 18.

Abstract

MicroRNA-92a-3p (miR-92a-3p) derives from the oncogenic miR-17/92 cluster and its highly homologous miR-106a/363 cluster. miR-92a-3p regulates the expression of key transcription factors such as HIF1 and inhibits SOCS1 to enhance the anti-apoptotic STAT3/IL6 signaling pathway. In this study, we assessed the putative usefulness of miR-92a-3p as a prognostic and/or diagnostic biomarker in chronic lymphocytic leukemia (CLL). For this purpose, total RNA was extracted from mononuclear cells isolated from the peripheral blood of 88 CLL patients and 36 non-leukemic blood donors, was polyadenylated and reversely transcribed. miR-92a-3p expression was quantified using an accurate qPCR method. miR-92a-3p levels were significantly lower in peripheral blood mononuclear cells of CLL patients. Overall survival (OS) analysis revealed that high miR-92a-3p expression predicts significantly prolonged OS of CLL patients. Interestingly, miR-92a-3p overexpression remains a significant prognosticator in subgroups of CLL patients with distinct prognosis. In conclusion, miR-92a-3p overexpression is a potential surrogate biomarker of favorable outcome of CLL patients.

Keywords: CLL; favorable prognosis; hematological malignancy; microRNA; prognostic biomarker; tumor marker.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor*
  • Case-Control Studies
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Kaplan-Meier Estimate
  • Leukemia, Lymphocytic, Chronic, B-Cell / diagnosis
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / mortality*
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Mutation
  • Prognosis
  • Proportional Hazards Models

Substances

  • Biomarkers, Tumor
  • Immunoglobulin Heavy Chains
  • MIRN92 microRNA, human
  • MicroRNAs