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microRNA-451-modulated hnRNP A1 takes a part in granulocytic differentiation regulation and acute myeloid leukemia

Li Song1, Hai-Shuang Lin1, Jia-Nan Gong1

  • 1The State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.

Oncotarget
|September 15, 2017
PubMed

Insights

Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) over-expression is linked to acute myeloid leukemia (AML). Decreased hnRNP A1 promotes granulocytic differentiation by releasing inhibition on C/EBPα, revealing its role in AML development.

Area of Science:

  • Hematology
  • Molecular Biology
  • Cancer Research

Background:

  • Myelopoiesis regulation is complex; its deregulation can lead to acute myeloid leukemia (AML).
  • Heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was identified as abnormally over-expressed in AML patients through microarray data analysis.

Purpose of the Study:

  • To investigate the function and mechanisms of hnRNP A1 in myeloid development and its role in AML.
  • To elucidate the regulatory network involving hnRNP A1, C/EBPα, miR-451, and c-Myc in granulocytic differentiation and AML.

Main Methods:

  • Analysis of AML cDNA microarray data (GSE2191).
  • Monitoring hnRNP A1 expression during granulocytic differentiation in cell lines (ATRA-induced-NB4, HL-60) and hematopoietic stem/progenitor cells.
  • Function-loss and gain experiments to determine hnRNP A1's inhibitory role on C/EBPα.
  • Investigating the regulatory effect of miR-451 on hnRNP A1 and the impact of hnRNP A1 on c-Myc expression.

Main Results:

  • hnRNP A1 expression gradually decreased during granulocytic differentiation.
  • hnRNP A1 inhibits granulocytic differentiation by suppressing C/EBPα expression.
  • Reduced hnRNP A1 allows increased C/EBPα, promoting differentiation.
  • miR-451 promotes differentiation by down-regulating hnRNP A1.
  • hnRNP A1 positively regulates c-Myc expression.

Conclusions:

  • hnRNP A1 plays a crucial inhibitory role in normal granulopoiesis.
  • A feedback loop involving c-Myc, miR-451, and hnRNP A1 is implicated in AML development.
  • Understanding hnRNP A1's mechanisms offers potential therapeutic targets for AML.
Keywords:
C/EBPαacute myeloid leukemia (AML)granulocytic differentiationhnRNP A1microRNA-451

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