title: CIAPIN1 targets Na+/H+ exchanger 1 to mediate K562 chronic myeloid leukemia cells' differentiation via ERK1/2 signaling pathway.
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.
authors.affiliation: 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.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Hairui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Chijuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Hongju
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yani
authors.initials: Y
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Yongxin
authors.initials: Y
authors.lastname: Ru
authors.affiliation: 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.
authors.forename: Haoyue
authors.initials: H
authors.lastname: Liang
authors.affiliation: 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.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Li
authors.affiliation: 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: pang@ihcams.ac.cn.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Pang
mesh_terms: D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006098:Granulocytes / Q000187:drug effects / Q000502:physiology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D019891:Leukopoiesis / Q000187:drug effects / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000235:genetics*; D013450:Sulfones / Q000494:pharmacology
chemical_list: C489114:CIAPIN1 protein, human; D027682:Cation Transport Proteins; D006146:Guanidines; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C093373:cariporide
keywords: CIAPIN1; Differentiation; ERK1/2; K562; Na(+)/H(+) exchanger 1