MiR-30e induces apoptosis and sensitizes K562 cells to imatinib treatment via regulation of the BCR-ABL protein

Oshrat Hershkovitz-Rokah, Shira Modai, Metsada Pasmanik-Chor, Amos Toren, Noam Shomron, Pia Raanani, Ofer Shpilberg, Galit Granot

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

Chronic myeloid leukemia (CML) is a disorder of hematopoietic stem cell carrying the Philadelphia (Ph) chromosome and an oncogenic BCR-ABL fusion gene. Tyrosine kinase inhibitors (TKIs) of the BCR-ABL kinase are the treatment of choice for CML patients. Imatinib was the first TKI used in clinical practice with excellent results. MicroRNAs (miRNAs) are short non-coding regulatory RNAs that control gene expression and play an important role in cancer development and progression. Aberrant miRNA expression profiles have been shown to be characteristic of many cancers. Here, we demonstrate that miR-30e is expressed at low levels in CML cell lines and patient samples. Bioinformatics analysis reveals a putative target site for miR-30e in the 3'-untranslated region (UTR) of the ABL gene. In agreement, luciferase assay verified that miR-30e directly targets ABL. Enforced expression of miR-30e in K562 cells suppressed proliferation and induced apoptosis of these cells and sensitized them to imatinib treatment. These findings strongly suggest that miR-30e acts as a tumor suppressor by downregulating BCR-ABL expression. Up-regulation of miR-30e in CML cells may therefore have a therapeutic efficacy against this disease.

Original languageEnglish
Pages (from-to)597-605
Number of pages9
JournalCancer Letters
Volume356
Issue number2
DOIs
StatePublished - 28 Jan 2015
Externally publishedYes

Keywords

  • Apoptosis
  • BCR-ABL
  • CML
  • Imatinib
  • MiR-30e

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'MiR-30e induces apoptosis and sensitizes K562 cells to imatinib treatment via regulation of the BCR-ABL protein'. Together they form a unique fingerprint.

Cite this