Total Platelet Transcriptomics and Its Network Analysis by RNA-Seq and miRNA-Seq and PCA Application in Essential Thrombocythaemia

Acta Haematol. 2021;144(3):337-344. doi: 10.1159/000510459. Epub 2020 Nov 23.

Abstract

Differentiating the aetiology of thrombocytosis is limited yet crucial in patients with essential thrombocythaemia (ET). MicroRNAs (miRNAs) regulate haematopoiesis and lineage commitment; aberrant expression of miRNAs plays an important role in myeloproliferative neoplasms. However, the miRNA profile has been poorly explored in ET patients compared to patients with reactive thrombocytosis (RT). A total of 9 samples, including 5 ET patient samples, 2 RT patient samples, and 2 healthy control samples, were analysed in this study. We produced 81.43 million reads from transcripts and 59.60 million reads from small RNAs. We generated a comprehensive miRNA-mRNA regulatory network and identified unique 14 miRNA expression patterns associated with ET. Among the 14 miRNAs, miR-1268a was downregulated in ET and showed an inverse correlation with its 8 putative target genes, including genes associated with thrombus formation and platelet activation (CDH6, EHD2, FUT1, KIF26A, LINC00346, PTPRN, SERF1A, and SLC6A9). Principal component analysis (PCA) showed ET and non-ET groups well clustered in space, suggesting each group had a distinctive expression pattern of mRNAs and miRNAs. These results suggest that the significant dysregulation of miR-1268a and its 8 target genes could be a unique expression of platelet mi-RNAs and miRNA/mRNA regulatory network in ET patients.

Keywords: Essential thrombocythaemia; MicroRNA; Transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Platelets / cytology
  • Blood Platelets / metabolism
  • Case-Control Studies
  • Cluster Analysis
  • Down-Regulation
  • Gene Regulatory Networks
  • Humans
  • Janus Kinase 2 / genetics
  • MicroRNAs / chemistry*
  • MicroRNAs / metabolism
  • Platelet Activation / genetics
  • Polymorphism, Single Nucleotide
  • Principal Component Analysis
  • RNA / chemistry*
  • RNA / metabolism
  • RNA-Seq
  • Thrombocythemia, Essential / metabolism
  • Thrombocythemia, Essential / pathology*
  • Transcriptome*

Substances

  • MicroRNAs
  • RNA
  • JAK2 protein, human
  • Janus Kinase 2