CIAPIN1 targets Na+/H+ exchanger 1 to mediate K562 chronic myeloid leukemia cells' differentiation via ERK1/2 signaling pathway

Jian Wang; Hua Xu; Hairui Zhang; Qi Wang; Chijuan Wang; Hongju Zhang; Yani Lin; Yongxin Ru; Haoyue Liang; Qinghua Li; Tianxiang Pang

doi:10.1016/j.leukres.2014.06.013

CIAPIN1 targets Na+/H+ exchanger 1 to mediate K562 chronic myeloid leukemia cells' differentiation via ERK1/2 signaling pathway

Leuk Res. 2014 Sep;38(9):1117-25. doi: 10.1016/j.leukres.2014.06.013. Epub 2014 Jul 5.

Authors

Jian Wang¹, Hua Xu¹, Hairui Zhang¹, Qi Wang¹, Chijuan Wang¹, Hongju Zhang¹, Yani Lin¹, Yongxin Ru¹, Haoyue Liang¹, Qinghua Li¹, Tianxiang Pang²

Affiliations

¹ State key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road 288, Tianjin 300020, China.
² State key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road 288, Tianjin 300020, China. Electronic address: [email protected].

PMID: 25043809
DOI: 10.1016/j.leukres.2014.06.013

Abstract

CIAPIN1 (cytokine-induced antiapoptotic inhibitor 1) was recently identified as an essential downstream effector of the Ras signaling pathway. However, its potential role in regulating myeloid differentiation remains unclear. In this study, we found depletion of CIAPIN1 by shRNAs led to granulocytic differentiation of K562 cells. Meanwhile, the decrease of NHE1 and up-regulation of phosphorylated ERK1/2 were observed after CIAPIN1 depletion. Interestingly, targeted inhibition of NHE1 further promoted the differentiation of K562 cells with CIAPIN1 silencing. Accordingly, ectopic expression of NHE1 reversed this phenotype. Furthermore, ERK1/2 inhibition with the chemical inhibitor, PD98059, abolished CIAPIN1 silencing-induced differentiation of K562 cells after NHE1 inhibition. Thus, our results revealed important mechanism that CIAPIN1 targeted NHE1 to mediate differentiation of K562 cells via ERK1/2 pathway. Our findings implied CIAPIN1 and NHE1 could be new targets in developing therapeutic strategies against leukemia.

Keywords: CIAPIN1; Differentiation; ERK1/2; K562; Na(+)/H(+) exchanger 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cation Transport Proteins / antagonists & inhibitors
Cation Transport Proteins / genetics*
Cell Differentiation / drug effects
Cell Differentiation / genetics*
Gene Expression Regulation, Leukemic / drug effects
Gene Knockdown Techniques
Granulocytes / drug effects
Granulocytes / physiology
Guanidines / pharmacology
Humans
Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
Intracellular Signaling Peptides and Proteins / physiology*
K562 Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
Leukopoiesis / drug effects
Leukopoiesis / genetics
MAP Kinase Signaling System / drug effects
MAP Kinase Signaling System / physiology*
RNA, Small Interfering / pharmacology
Sodium-Hydrogen Exchanger 1
Sodium-Hydrogen Exchangers / antagonists & inhibitors
Sodium-Hydrogen Exchangers / genetics*
Sulfones / pharmacology

Substances

CIAPIN1 protein, human
Cation Transport Proteins
Guanidines
Intracellular Signaling Peptides and Proteins
RNA, Small Interfering
SLC9A1 protein, human
Sodium-Hydrogen Exchanger 1
Sodium-Hydrogen Exchangers
Sulfones
cariporide