HnRNP K contributes to drug resistance in acute myeloid leukemia through the regulation of autophagy

Exp Hematol. 2016 Sep;44(9):850-856. doi: 10.1016/j.exphem.2016.04.014. Epub 2016 May 4.

Abstract

The goal of this study was to explore the role of heterogeneous nuclear ribonucleoprotein K (hnRNP K) in drug resistance through the regulation of autophagy in acute myeloid leukemia (AML). First, we used fluorescence quantitative polymerase chain reaction (PCR) to verify the connection between the expression level of hnRNP K and the level of drug resistance in AML. We then used Western blotting to determine the expression level of the autophagy-related proteins microtubule-associated protein light chain 3 I and II (LC3 I/II) after the modulation of hnRNP K by ribonucleic acid (RNA) interference. Finally, an analysis of adriamycin drug sensitivity was conducted before and after the modulation of hnRNP K expression. hnRNP K and LC3 I/II were significantly overexpressed in the bone marrow of nonremission patients and in drug-resistant cell lines; however, the expression of LC3 I/II was decreased when the expression of hnRNP K was reduced and drug sensitivity to adriamycin could be restored. hnRNP K may be involved in the development of adriamycin resistance in AML through the regulation of autophagy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Autophagy / drug effects*
  • Autophagy / genetics*
  • Cell Line, Tumor
  • Child
  • Child, Preschool
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression
  • Genotype
  • Heterogeneous-Nuclear Ribonucleoprotein K / genetics*
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Microtubule-Associated Proteins / genetics
  • RNA Interference
  • RNA, Small Interfering / genetics

Substances

  • Antineoplastic Agents
  • Heterogeneous-Nuclear Ribonucleoprotein K
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • RNA, Small Interfering