High expression of long non-coding RNA H19 is required for efficient tumorigenesis induced by Bcr-Abl oncogene

FEBS Lett. 2014 May 2;588(9):1780-6. doi: 10.1016/j.febslet.2014.03.038. Epub 2014 Mar 28.

Abstract

Dysregulation of non-coding RNA H19 has been observed in various tumors. However, it remains unknown whether H19 is involved in Bcr-Abl-induced leukemia. Here, we demonstrate a critical requirement for H19 in Bcr-Abl-mediated tumorigenesis. H19 was highly expressed in Bcr-Abl-transformed cell lines and primary cells derived from patients in a Bcr-Abl kinase-dependent manner. Silencing H19 expression sensitized leukemic cells to undergo imatinib-induced apoptosis and inhibited Bcr-Abl-induced tumor growth. Furthermore, H19 was shown to be regulated by c-Myc in Bcr-Abl-expressing cells. These results reveal an important role H19 plays in Bcr-Abl-mediated transformation and provide novel insights into complex mechanisms underlying Bcr-Abl-induced cancers.

Keywords: Bcr-Abl; H19; Long non-coding RNA; Tumorigenesis; c-Myc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / metabolism
  • Female
  • Fusion Proteins, bcr-abl / genetics*
  • Fusion Proteins, bcr-abl / metabolism
  • Gene Expression
  • Gene Expression Regulation, Leukemic
  • Humans
  • Jurkat Cells
  • K562 Cells
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism

Substances

  • H19 long non-coding RNA
  • MYC protein, human
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • Fusion Proteins, bcr-abl