title: MiR-124-3p/B4GALT1 axis plays an important role in SOCS3-regulated growth and chemo-sensitivity of CML.
abstract: Abnormal expression of SOCS3 has been implicated in myeloproliferative neoplasms, but the role of SOCS3 in the pathogenesis of leukemia remains largely unknown. Here, we examined the function of SOCS3 in the growth and chemo-sensitivity of chronic myeloid leukemia (CML) and explored the involved mechanisms.
  
  
  
  Expression levels of SOCS3 in several leukemia cell lines and bone marrow mononuclear cells (BMNCs) from CML patients were determined using quantitative real-time PCR (qPCR) and Western blotting (WB). The roles of SOCS3 in the proliferation, apoptosis, and drug resistance of CML cells were examined by clonogenic progenitor cell assay, flow cytometry, and CCK-8 assay. A detailed analysis of the underlying mechanism of SOCS3 in K562 cells was performed using the Human HT-12 v4 Expression BeadChip, which has more than 48000 gene probes including 600 microRNAs (miRNA) probes. The correlation between the mRNA expression of SOCS3 and miR-124-3p in BMNCs from 30 CML patients was tested by qPCR and analyzed by Pearson correlation and linear regression analysis. The potential target of miR-124-3p in CML cells was explored using the luciferase reporter assay, qPCR, and WB. The effect of SOCS3 on the miR-124-3p/B4GALT1 axis was investigated by qPCR, WB, CCK-8 assay, and tumorigenicity assays in nude mice.
  
  
  
  SOCS3 was down-regulated in CML cell lines and most of BMNCs from CML patients, and the expression level of SOCS3 was associated with the inhibition of cell proliferation and drug resistance of CML cells. Over-expression of SOCS3 in K562 cells inhibited the expression of leukemia-specific genes and promoted the expression of some miRNAs, among which miR-124-3p was the highest. SOCS3 over-expression enhanced the expression of miR-124-3p and vice versa. The mRNA expression of miR-124-3p and SOCS3 in BMNCs from 30 CML patients was positively correlated. Consistently, the tumor suppressing effects of SOCS3 were partially neutralized by the miR-124-3p inhibitor. B4GALT1 was downstream of miR-124-3p and regulated by SOCS3/miR-124-3p in vitro. Furthermore, SOCS3 over-expression could inhibit the growth and B4GALT expression of K562 cells in vivo.
  
  
  
  SOCS3/miR-124-3p/B4GALT1 axis plays an important role in the pathogenesis of CML.
authors: Department of Neurosurgery, The First Affiliated Hospital of Chinese PLA General Hospital, 51 Fushi Road, Beijing, 100048, People's Republic of China.
authors: Yu-Xiao
authors: YX
authors: Liu
authors: Department of Hematology, Chinese PLA General Hospital, Laoshan Branch, No. 401, Qingdao, 266100, People's Republic of China.|Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People's Republic of China.
authors: Li
authors: L
authors: Wang
authors: Genetic Laboratory of Development and Diseases, Beijing Institute of Biotechnology, Beijing, 100071, People's Republic of China.
authors: Wen-Jia
authors: WJ
authors: Liu
authors: Department of Neurosurgery, The First Affiliated Hospital of Chinese PLA General Hospital, 51 Fushi Road, Beijing, 100048, People's Republic of China.
authors: Hai-Tao
authors: HT
authors: Zhang
authors: Department of Neurosurgery, The First Affiliated Hospital of Chinese PLA General Hospital, 51 Fushi Road, Beijing, 100048, People's Republic of China. xuejh629@163.com.
authors: Jing-Hui
authors: JH
authors: Xue
authors: Department of Neurosurgery, The First Affiliated Hospital of Chinese PLA General Hospital, 51 Fushi Road, Beijing, 100048, People's Republic of China.
authors: Zhi-Wen
authors: ZW
authors: Zhang
authors: Department of Hematology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, People's Republic of China. gaochunji@hotmail.com.
authors: Chun-Ji
authors: CJ
authors: Gao
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005700:Galactosyltransferases / Q000187:drug effects / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008819:Mice, Nude; D035683:MicroRNAs / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: C509207:MIRN124 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C106644:SOCS3 protein, human; D000071223:Suppressor of Cytokine Signaling 3 Protein; D005700:Galactosyltransferases; C119701:beta-1,4-galactosyltransferase I
keywords: B4GALT1; Chemo-sensitivity; Leukemogenesis; SOCS3; miR-124