Alpha-2, 3-sialyltransferases regulate the multidrug resistance of chronic myeloid leukemia through miR-4701-5p targeting ST3GAL1

Lab Invest. 2016 Jul;96(7):731-40. doi: 10.1038/labinvest.2016.50. Epub 2016 Apr 18.

Abstract

The aberrant sialylation profile on the surface of leukemia cells has been recognized for its potential diagnostic value towards assessing leukemia multidrug resistance (MDR). MicroRNAs as endogenous regulators of gene expression have been implicated in treating MDR. In this study, we describe the differential expressional profiles of α-2, 3-sialyltransferases (ST) and miR-4701-5p in three pairs of chronic myeloid leukemia (CML) cell lines and 48 clinical samples of bone marrow mononuclear cells from CML patients. The altered expression level of ST3GAL1 was found corresponding to the drug-resistant phenotype (with and without adriamycin resistance) of CML cell lines both in vitro and in vivo. Further the results showed that miR-4701-5p directly targeted ST3GAL1 to reduce CML cells resistance to multiple chemotherapeutics in vitro and to convert tumor cells from adriamycin resistant to susceptible in vivo of mice. These results indicate that differential expression of α-2,3 ST is involved in MDR of CML, and that miR-4701-5p regulates the susceptibility of CML cells to multiple drugs, at least in part, through targeting ST3GAL1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Cell Line, Tumor
  • Doxorubicin / pharmacology
  • Drug Resistance, Multiple / genetics
  • Drug Resistance, Multiple / physiology
  • Drug Resistance, Neoplasm / genetics
  • Drug Resistance, Neoplasm / physiology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • K562 Cells
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Middle Aged
  • Sialyltransferases / antagonists & inhibitors
  • Sialyltransferases / genetics*
  • Sialyltransferases / metabolism*
  • Xenograft Model Antitumor Assays
  • Young Adult

Substances

  • MIRN4701 microRNA, human
  • MicroRNAs
  • Doxorubicin
  • Sialyltransferases
  • beta-galactoside alpha-2,3-sialyltransferase