title: miR-26a and miR-214 down-regulate expression of the PTEN gene in chronic lymphocytic leukemia, but not PTEN mutation or promoter methylation.
abstract: We previous found the expression level of PTEN was low in the chronic lymphocytic leukemia (CLL) patients. To assess the pathogenic contribution of the low expression of PTEN, we determined PTEN-regulating miRNA interference, PTEN promoter methylation and PTEN gene mutation condition in CLL. One hundred and fifty-four previously untreated CLL patients and 200 cases of healthy controls were sequenced in exons 5-9 of PTEN. None of single nucleotide polymorphism site or mutation was detected in the coding sequences of those exons. Methylation of PTEN promoter was found in one (1.33%) of the 75 patients with CLL, but none of the 25 age-matched control subjects. We found that PTEN was a potential target of miR-26a and miR-214, which had been confirmed following dual-luciferase reporter assays, reverse transcription polymerase chain reaction and Western blotting. High expression of miR-26a was associated with advanced Binet stage (P=0.012), p53 aberrations (P=0.014) and inferior time to first treatment (P=0.038), and high expression of miR-214 was only associated with p53 aberrations (P=0.041). Inhibition of miR-26a or miR-214 could induce more apoptosis in primary cultured CLL cells. These findings support miR-26a and miR-214 down-regulate expression of PTEN in CLL, but not PTEN mutation or promoter methylation.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.|Department of Hematology, Wuxi People Hospital Affiliated of Nanjing Medical University, Wuxi, China.
authors.forename: Zhi-Jian
authors.initials: ZJ
authors.lastname: Zou
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Ji
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Run
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Tian
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Li
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D019175:DNA Methylation; D015536:Down-Regulation; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; D016159:Tumor Suppressor Protein p53; C547397:MIRN214 microRNA, human; C528163:MIRN26 microRNA, human; C494929:PTEN protein, human