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TET1-mediated microRNA-188-5p promoter hydroxymethylation regulates PTEN/PI3K/AKT signaling pathway in acute myeloid

Nadan Lu1, Xiaoyi Wang1, Weilin Wang1

  • 1Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, PR China.

Archives of Biochemistry and Biophysics
|January 22, 2023
PubMed
Abstract

Insights

MicroRNA-188-5p (miR-188-5p) promotes Adriamycin (ADM) resistance in acute myeloid leukemia (AML) by inhibiting PTEN and activating the PI3K/AKT pathway. Inhibiting miR-188-5p can re-sensitize AML cells to ADM chemotherapy.

Area of Science:

  • Hematology
  • Molecular Biology
  • Oncology

Background:

  • Acute myeloid leukemia (AML) is a common blood cancer.
  • Drug resistance to chemotherapy, like Adriamycin (ADM), is a major challenge in AML treatment.

Purpose of the Study:

  • To investigate the role of microRNA-188-5p (miR-188-5p) in mediating ADM resistance in AML.
  • To elucidate the molecular mechanisms behind miR-188-5p-induced ADM resistance.

Main Methods:

  • Bioinformatic screening of differentially expressed miRNAs.
  • Evaluation of miR-188-5p expression in AML cells.
  • Establishment of ADM-resistant AML cell lines.
  • Inhibition of miR-188-5p and TET1 to assess drug sensitivity.
  • ChIP and dual-luciferase assays to determine target interactions.
  • In vitro and in vivo rescue experiments.

Main Results:

  • miR-188-5p was highly expressed in AML cells and its inhibition sensitized cells to ADM.
  • TET1 inhibition reduced miR-188-5p expression.
  • miR-188-5p directly targets PTEN, inhibiting its expression.
  • PTEN inhibition activated the PI3K/AKT signaling pathway, conferring ADM resistance.

Conclusions:

  • TET1 upregulates miR-188-5p via promoter hydroxymethylation.
  • miR-188-5p induces ADM resistance in AML by suppressing PTEN and activating the PI3K/AKT pathway.
Keywords:
Acute myeloid leukemiaAdriamycinPTEN/PI3K/AKT axisTET1microRNA-188-5p

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