The c-Myc-regulated miR-17-92 cluster mediates ATRA-induced APL cell differentiation

Xibao Yu1,2, Yanyun Hu2, Yifan Wu2

  • 1Department of Experimental Research, Sun Yat-sen University Cancer Center, State Key Laboratory Oncology in South China, Guangzhou, China.

Abstract

Insights

The miR-17-92 microRNA cluster is abnormally expressed in acute promyelocytic leukemia (APL) and blocks cell differentiation. This cluster is regulated by c-Myc during all-trans-retinoic acid treatment.

Area of Science:

  • Hematology
  • Molecular Biology
  • Oncology

Background:

  • Acute promyelocytic leukemia (APL) treatment with all-trans-retinoic acid (ATRA) has advanced, but mechanisms remain unclear.
  • The miR-17-92 microRNA cluster impacts cell survival, proliferation, and apoptosis.
  • The role and regulation of miR-17-92 in APL are not well understood.

Purpose of the Study:

  • To investigate the expression and role of the miR-17-92 cluster in APL.
  • To explore the relationship between miR-17-92, c-Myc, and ATRA-induced differentiation in APL.

Main Methods:

  • Quantitative reverse transcription PCR (qRT-PCR) to analyze miR-17-92 expression.
  • Western blot to measure c-Myc expression.
  • Flow cytometry to assess cell differentiation via CD11b antigen expression.

Main Results:

  • miR-17-92 was upregulated in APL samples compared to healthy donors.
  • c-Myc and miR-17-92 expression decreased during ATRA-induced differentiation of NB4 cells.
  • miR-17-92 is directly regulated by c-Myc during APL cell differentiation.
  • Overexpression of miR-17-5p inhibited ATRA-induced differentiation.

Conclusions:

  • Abnormal miR-17-92 cluster expression contributes to the differentiation block in APL blast cells.
  • miR-17-92 is identified as a c-Myc target gene during ATRA-induced granulocytic differentiation.

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