title: The malignancy suppression role of miR-23a by targeting the BCR/ABL oncogene in chromic myeloid leukemia.
abstract: The aim of this study was to investigate the role and mechanism of miR-23a in the regulation of BCR/ABL and to provide a new prognostic biomarker for chronic myeloid leukemia (CML). The expression levels of miR-23a and BCR/ABL were assessed in 42 newly diagnosed CML patients, 37 CML patients in first complete remission and 25 healthy controls. Quantitative real-time PCR, western blot analysis and colony formation assay were used to evaluate changes induced by overexpression or inhibition of miR-23a or BCR/ABL. MiR-23a mimic or negative control mimic was transfected into a CML cell line (K562) and two lung cancer cell lines (H157 and SKMES1) using Lipofectamine 2000, and the cells were used for real-time reverse transcription-PCR (RT-PCR) and western blot analysis. We found that the downregulation of miR-23a expression was a frequent event in both leukemia cell lines and primary leukemic cells from patients with de novo CML. The microarray results showed that most of the CML patients expressed high levels of BCR/ABL and low levels of miR-23a. Real-time RT-PCR and western blot analysis showed that the BCR/ABL levels in miR-23a-transfected cells were lower than those in the control groups. Ectopic expression of miR-23a in K562 cells led to cellular senescence. Moreover, when K562 cells were treated with 5-aza-2'-deoxycytidine, a DNA methylation inhibitor, BCR/ABL expression was upregulated, which indicates epigenetic silencing of miR-23a in leukemic cells. BCR/ABL and miR-23a expressions were inversely related to CML, and BCR/ABL expression was regulated by miR-23a in leukemic cells. The epigenetic silencing of miR-23a led to derepression of BCR/ABL expression, and consequently contributes to CML development and progression.
authors.affiliation: Clinical Research Center, Affiliated Hospital of Guangdong Medical College, Guangdong province, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Xishan
authors.affiliation: Department of Nuclear Medicine, Weifang People's Hospital, Weifang, Shandong, P.R. China.
authors.forename: L
authors.initials: L
authors.lastname: Xianjun
authors.affiliation: Clinical Research Center, Affiliated Hospital of Guangdong Medical College, Guangdong province, China.
authors.forename: L
authors.initials: L
authors.lastname: Ziying
authors.affiliation: Department of Nuclear Medicine, Weifang People's Hospital, Weifang, Shandong, P.R. China.
authors.forename: C
authors.initials: C
authors.lastname: Guangxin
authors.affiliation: Clinical Research Center, Affiliated Hospital of Guangdong Medical College, Guangdong province, China.
authors.forename: L
authors.initials: L
authors.lastname: Gang
mesh_terms: D020413:3' Untranslated Regions; D000293:Adolescent; D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000494:pharmacology; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000235:genetics; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D034622:RNA Interference; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D001374:Azacitidine; D016044:Fusion Proteins, bcr-abl; D020780:Matrix Metalloproteinase 9; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C552430:MIRN23a microRNA, human