Upregulation of long noncoding RNA MIAT in aggressive form of chronic lymphocytic leukemias

Oncotarget. 2016 Aug 23;7(34):54174-54182. doi: 10.18632/oncotarget.11099.

Abstract

Long noncoding RNAs (lncRNAs) are non-proten-coding transcripts of more than 200 nucleotides generated by RNA polymerase II and their expressions are tightly regulated in cell type specific- and/or cellular differential stage specific- manner. MIAT, originally isolated as a candidate gene for myocardial infarction, encodes lncRNA (termed MIAT). Here, we determined the expression level of MIAT in established leukemia/lymphoma cell lines and found its upregulation in lymphoid but not in myeloid cell lineage with mature B cell phenotype. MIAT expression level was further determined in chronic lymphocytic leukemias (CLL), characterized by expansion of leukemic cells with mature B phenotype, to demonstrate relatively high occurrence of MIAT upregulation in aggressive form of CLL carrying either 17p-deletion, 11q-deletion, or Trisomy 12 over indolent form carrying 13p-deletion. Furthermore, we show that MIAT constitutes a regulatory loop with OCT4 in malignant mature B cell, as was previously reported in mouse pulripotent stem cell, and that both molecules are essential for cell survival.

Keywords: OCT4; cell apoptosis; chronic lymphocytic leukemia; long noncoding RNA MIAT; non-Hodgkin’s lymphoma.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Octamer Transcription Factor-3 / physiology
  • RNA, Long Noncoding / physiology*
  • Up-Regulation

Substances

  • Miat long non-coding RNA
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • RNA, Long Noncoding