title: Alterations of deadenylase expression in acute leukemias: evidence for poly(a)-specific ribonuclease as a potential biomarker.
abstract: OBJECTIVE
  The degradation of mRNA is a key process in the control of gene expression correlated to anomalous cell proliferation. The rate-limiting step of mRNA degradation is the removal of the poly(A) tail by deadenylases. However, studies on deadenylase expression in cancer are limited. Herein, we analyzed the expression of several deadenylases from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).
  
  
  METHODS
  Clinical samples from patients diagnosed with ALL and AML were the source of leukemic cells. Extracts from leukemic and control cells were analyzed for deadenylase mRNA levels using qRT-PCR, and the protein levels of PARN and CNOT7 deadenylases using immunoblotting.
  
  
  RESULTS
  RT-PCR analysis revealed altered expression for CNOT6, CNOT6L, CNOT7 and PARN deadenylases. The most significant alterations were observed for PARN and CNOT7 mRNA levels, which also reflect on the cognate protein level. Further analysis revealed that a significant amount of PARN is phosphorylated in ALL.
  
  
  CONCLUSIONS
  We show that the expression of several deadenylases in acute leukemias is altered. The increase of PARN expression and the alteration of its phosphorylation status indicate important regulatory events. These data suggest that the role of deadenylases as auxiliary biomarkers and therapeutic targets should be meticulously investigated.
authors.affiliation: Department of Biochemistry and Biotechnology, University of Thessaly, Larissa, Greece.
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Maragozidis
authors.forename: Maria
authors.initials: M
authors.lastname: Karangeli
authors.forename: Maria
authors.initials: M
authors.lastname: Labrou
authors.forename: Georgia
authors.initials: G
authors.lastname: Dimoulou
authors.forename: Konstantia
authors.initials: K
authors.lastname: Papaspyrou
authors.forename: Eralda
authors.initials: E
authors.lastname: Salataj
authors.forename: Spyridon
authors.initials: S
authors.lastname: Pournaras
authors.forename: Panagiota
authors.initials: P
authors.lastname: Matsouka
authors.forename: Konstantinos I
authors.initials: KI
authors.lastname: Gourgoulianis
authors.forename: Nikolaos A A
authors.initials: NA
authors.lastname: Balatsos
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D005095:Exoribonucleases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins; D012260:Ribonucleases / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005095:Exoribonucleases; D012333:RNA, Messenger; D012097:Repressor Proteins; D012260:Ribonucleases; D014157:Transcription Factors; C521732:CNOT6L protein, human; C545829:CNOT7 protein, human; C534418:cNOT6 protein, human; C445084:mRNA deadenylase