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Preparation and In Vitro Characterization of Magnetized miR-modified Endothelial Cells
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miR-181a down-regulates MAP2K1 to enhance adriamycin sensitivity in leukemia HL-60 cells

J-J Wang1, J-P Yu

  • 1Department of Laboratory, Nuclear Industry 215 Hospital of Shaanxi Province, Xianyang, Shaanxi, China. yuyujianping@126.com.

European Review for Medical and Pharmacological Sciences
|April 10, 2019
PubMed
Abstract

Insights

MicroRNA-181a (miR-181a) targets MAPK kinase 1 (MEK1/MAP2K1) in leukemia cells. Increasing miR-181a combats drug resistance by reducing MEK1, inhibiting proliferation, and promoting apoptosis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • MAPK kinase 1 (MEK1/MAP2K1) is crucial for cell proliferation and apoptosis, and its abnormal expression is linked to leukemia.
  • Bioinformatics analysis suggests a regulatory relationship between microRNA-181a (miR-181a) and MAP2K1.

Purpose of the Study:

  • To investigate the role of miR-181a in regulating MAP2K1 expression in leukemia.
  • To determine the effects of miR-181a on leukemic cell proliferation, apoptosis, and adriamycin (ADM) resistance.

Main Methods:

  • Dual luciferase reporter gene assay to confirm the miR-181a and MAP2K1 interaction.
  • Establishment of an ADM-resistant HL-60/ADM cell line for expression analysis.
  • In vitro culture and treatment of HL-60/ADM cells with miR-181a mimic or control.
  • Assessment of protein expression (MAP2K1, p-MAP2K1, p-ERK) via Western blot, apoptosis via flow cytometry, and proliferation via EdU staining.

Main Results:

  • A targeted regulatory relationship between miR-181a and MAP2K1 mRNA was confirmed.
  • HL-60/ADM cells exhibited significantly lower miR-181a and higher MAP2K1 expression compared to HL-60 cells.
  • Upregulation of miR-181a in HL-60/ADM cells reduced MAP2K1, p-MAP2K1, and p-ERK levels, suppressed proliferation, and enhanced apoptosis.

Conclusions:

  • Reduced miR-181a and elevated MAP2K1 are associated with adriamycin resistance in leukemia.
  • Upregulating miR-181a inhibits leukemia cell proliferation, induces apoptosis, and overcomes ADM resistance by targeting the MAP2K1/ERK/MAPK pathway.

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