title: MicroRNA-100/99a, deregulated in acute lymphoblastic leukaemia, suppress proliferation and promote apoptosis by regulating the FKBP51 and IGF1R/mTOR signalling pathways.
abstract: BACKGROUND
  MicroRNAs alter multiple cell processes and thus influence tumour carcinogenesis and progression. MiR-100 and miR-99a have been reported to be aberrantly expressed in acute leukaemia. In this study, we focused on their functions in acute lymphoblastic leukaemia (ALL) and the molecular networks in which they are involved.
  
  
  METHODS
  MiR-100 and miR-99a expression levels were measured in acute leukaemia patients by qRT-PCR. Kaplan-Meier analysis and log-rank tests were used to calculate the survival rate. Three human ALL cell lines were studied. Apoptosis and proliferation were analysed using siRNA transfection, western blot and flow cytometry.
  
  
  RESULTS
  In vivo, miR-100 and miR-99a were down-regulated in 111 ALL patients, especially in high-risk groups; their expression levels were correlated with the patient's 5-year survival. In vitro, the restoration of miR-100 and miR-99a in ALL cells suppressed cell proliferation and increased dexamethasone-induced cell apoptosis. Ectopic expression of miR-100 and miR-99a targeted FK506-binding protein 51 (FKBP51) and, in turn, influenced glucocorticoid receptor (GR) activity. Meanwhile, miR-100 and miR-99a overexpression inhibited the expression of IGF1R and mTOR and their downstream oncogene MCL1.
  
  
  CONCLUSIONS
  MiR-100 and miR-99a have critical roles in altering cellular processes by targeting both the FKBP51 and IGF1R/mTOR signalling pathways in vitro and might represent a potential novel strategy for ALL treatment.
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, School of Life Science, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Li
authors.forename: X-Q
authors.initials: XQ
authors.lastname: Luo
authors.forename: B-W
authors.initials: BW
authors.lastname: Han
authors.forename: F-T
authors.initials: FT
authors.lastname: Duan
authors.forename: P-P
authors.initials: PP
authors.lastname: Wei
authors.forename: Y-Q
authors.initials: YQ
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002648:Child; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D019169:Jurkat Cells; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000099159:Tacrolimus Binding Protein 5
chemical_list: D035683:MicroRNAs; D017526:Receptor, IGF Type 1; D058570:TOR Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C544266:MIRN100 microRNA, human; C561679:MIRN99 microRNA, human; C546842:MTOR protein, human
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