Oncotarget

Research Papers:

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

Li Song, Hai-Shuang Lin, Jia-Nan Gong, Hua Han, Xiao-Shuang Wang, Rui Su, Ming-Tai Chen, Chao Shen, Yan-Ni Ma, Jia Yu and Jun-Wu Zhang _

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Oncotarget. 2017; 8:55453-55466. https://doi.org/10.18632/oncotarget.19325

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Abstract

Li Song1, Hai-Shuang Lin1, Jia-Nan Gong1, Hua Han2, Xiao-Shuang Wang1, Rui Su1, Ming-Tai Chen1, Chao Shen1, Yan-Ni Ma1, Jia Yu1 and Jun-Wu Zhang1

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

2Department of Obstetrics and Gynecology, Hebei General Hospital, Shijiazhuang 050051, China

Correspondence to:

Jun-Wu Zhang, email: [email protected]

Keywords: acute myeloid leukemia (AML), granulocytic differentiation, hnRNP A1, C/EBPα, microRNA-451

Received: April 11, 2017     Accepted: June 11, 2017     Published: July 18, 2017

ABSTRACT

Myelopoiesis is under the control of a complex network containing various regulation factors. Deregulation of any important regulation factors may result in serious consequences including acute myeloid leukemia (AML). In order to find out the genes that may take a part in AML development, we analyzed data from AML cDNA microarray (GSE2191) in the NCBI data pool and noticed that heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) is abnormally over-expressed in AML patients. Then we investigated the function and mechanisms of hnRNP A1 in myeloid development. A gradually decreased hnRNP A1 expression was detected during granulocytic differentiation in ATRA-induced-NB4 and HL-60 cells and cytokines-induced hematopoietic stem and progenitor cells. By function-loss and winning experiments we demonstrated hnRNP A1’s inhibition role via inhibiting expression of C/EBPα, a key regulator of granulocytic differentiation, in the granulocytic differentiation. During granulocytic differentiation the decrease of hnRNP A1 reduces inhibition on C/EBPα expression, and the increased C/EBPα promotes the differentiation. We also demonstrated that miR-451 promotes granulocytic differentiation via targeting to and down-regulating hnRNP A1, and hnRNP A1 positively regulates c-Myc expression. Summarily, our results revealed new function and mechanisms of hnRNP A1 in normal granulocytiesis and the involvement of a feed-back loop comprising c-Myc, miR-451 and hnRNP A1 in AML development.


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