Identification of post-transcriptional regulatory networks during myeloblast-to-monocyte differentiation transition

RNA Biol. 2015;12(7):690-700. doi: 10.1080/15476286.2015.1044194.

Abstract

Treatment of leukemia cells with 1,25-dihydroxyvitamin D3 may overcome their differentiation block and lead to the transition from myeloblasts to monocytes. To identify microRNA-mRNA networks relevant for myeloid differentiation, we profiled the expression of mRNAs and microRNAs associated to the low- and high-density ribosomal fractions in leukemic cells and in their differentiated monocytic counterpart. Intersection between mRNAs shifted across the fractions after treatment with putative target genes of modulated microRNAs showed a series of molecular networks relevant for the monocyte cell fate determination, as for example the post-transcriptional regulation of the Polo-like kinase 1 (PLK1) by miR-22-3p and let-7e-5p.

Keywords: AGO2, argonaute 2; AML; AML, acute myeloid leukemia; ECL methods, enhanced chemiluminescence methods; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GFP, green fluorescent protein; HPCs, haematopoietic progenitor cells; KPNA2, karyopherin α, 2; NBT assay, nitroblue tetrazolium assay; PLK1; PLK1, polo-like kinase 1; PMSF, phenylmethylsulfonyl fluoride; RAB10, member RAS oncogene family 10; RAB5C, member RAS oncogene family 5C; RT-qPCR, quantitative reverse transcription polymerase chain reaction; SF2A1, splicing factor 2A1; TFs, transcription factors; VitD3, 1,25-dihydroxyvitamin D3; miRNAs, microRNAs; microRNAs; myeloid differentiation; ribosomal/polysomal fractions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Cell Differentiation*
  • Cholecalciferol / metabolism
  • Gene Regulatory Networks*
  • Granulocyte Precursor Cells / cytology*
  • Granulocyte Precursor Cells / metabolism
  • HL-60 Cells
  • Humans
  • Leukemia / metabolism
  • MicroRNAs / metabolism
  • Monocytes / cytology*
  • Monocytes / metabolism
  • Polo-Like Kinase 1
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • RNA Processing, Post-Transcriptional*
  • RNA, Messenger / metabolism*

Substances

  • Cell Cycle Proteins
  • MIRN22 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • mirnlet7 microRNA, human
  • Cholecalciferol
  • Protein Serine-Threonine Kinases