title: MiR-362-5p promotes the malignancy of chronic myelocytic leukaemia via down-regulation of GADD45α.
abstract: MicroRNAs (miR, miRNAs) play pivotal roles in numerous physiological and pathophysiological contexts. We investigated whether miR-362-5p act as an oncogene in chronic myeloid leukaemia (CML) and aimed to understand its potential underlying mechanisms.
  
  
  
  We compared the miR-362-5p expression levels between CML and non-CML cell lines, and between fresh blood samples from CML patients and normal healthy controls using quantitative real-time PCR (qPCR). Cell counting kit-8 (CCK-8) and Annexin V-FITC/PI analyses were used to measure the effects of miR-362-5p on proliferation and apoptosis, and Transwell assays were used to evaluate migration and invasion. A xenograft model was used to examine in vivo tumourigenicity. The potential target of miR-362-5p was confirmed by a luciferase reporter assay, qPCR and western blotting. Involvement of the JNK1/2 and P38 pathways was investigated by western blotting.
  
  
  
  miR-362-5p was up-regulated in CML cell lines and fresh blood samples from CML patients, and was associated with Growth arrest and DNA damage-inducible (GADD)45α down-regulation. Inhibition of miR-362-5p simultaneously repressed tumour growth and up-regulated GADD45α expression in a xenograft model. Consistently, the knockdown of GADD45α expression partially neutralized the effects of miR-362-5p inhibition. Furthermore study suggested that GADD45α mediated downstream the effects of miR-362-5p, which might indirectly regulates the activation of the JNK1/2 and P38 signalling pathways.
  
  
  
  miR-362-5p acts as an oncomiR that down-regulates GADD45α, which consequently activates the JNK1/2 and P38 signalling. This finding provides novel insights into CML leukaemogenesis and may help identify new diagnostic and therapeutic targets.
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. yangpeng00812@163.com.|Department of Transfusion, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, PR China. yangpeng00812@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. nifang1203@126.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Ni
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. 443703883@qq.com.
authors.forename: Rui-Qing
authors.initials: RQ
authors.lastname: Deng
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. 414235163@qq.com.
authors.forename: Guo
authors.initials: G
authors.lastname: Qiang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. bananazh.ivy@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Haematology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, PR China. yangmz89@163.com.
authors.forename: Ming-Zhen
authors.initials: MZ
authors.lastname: Yang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. 409416935@qq.com.|Department of Clinical Medicine, Anhui Medical University, Hefei, Anhui, 230032, PR China. 409416935@qq.com.
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. youzhixu08@gmail.com.
authors.forename: You-Zhi
authors.initials: YZ
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. 23864775@qq.com.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. 869663530@qq.com.
authors.forename: Dan-Lei
authors.initials: DL
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. 269884236@qq.com.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. 2816393992@qq.com.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Kan
authors.affiliation: Department of Pathophysiology, School of Basic Medical Science, Anhui Medical University, 81 MeiShan Road, Hefei, Anhui, 230032, PR China. sywang@ahmu.edu.cn.
authors.forename: Si-Ying
authors.initials: SY
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D000097642:GADD45 Proteins
chemical_list: D018797:Cell Cycle Proteins; D035683:MicroRNAs; D009687:Nuclear Proteins; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C575475:MIRN361 microRNA, human