title: [microRNAs expression profile in acute promyelocytic leukemia cell differentiation induced by all-trans retinoic acid and arsenic trioxide].
abstract: OBJECTIVE
  To study the expression profile of microRNAs in acute promyelocytic leukemia (APL) cells during differentiation.
  
  
  METHODS
  Differentiation of APL cell line NB4 cells was induced by all-trans retinoic acid (ATRA) and arsenic trioxide (As2O3). Morphological and immunological assay was performed by Wright-Giemsa staining and flow-cytometric analysis of CD11b surface expression. During in vitro NB4 differentiation induced by ATRA and As2O3, microRNA expression profiles (miR-15b, miR-16, miR-34a, miR-107, miR-124a, miR-146, miR-155, miR-181a, miR-223, miR-342, let7c) were detected by real time RT-PCR, and the relative expression level of microRNAs were quantitatively analyzed by using 2(-ΔΔCt), and compared with that of control group. Meanwhile, the microRNA expression profiles were also detected in 15 newly diagnosed APL patients and 15 complete remission (CR) APL cases by real time RT-PCR, and the relative expression level of microRNA was quantitated by using 2(-ΔCt), and compared with that of control group (newly diagnosed APL as control group). These data were expressed as x(-) ± s, and differences between groups were examined using t test. P < 0.05 was considered statistically significant.
  
  
  RESULTS
  The expression levels of miR-15b, miR-16, miR-107, miR-223 and miR-342 in NB4 differentiation group were obviously up-regulated (3.40, 4.22, 5.41, 20.03 and 5.29 folds higher in ATRA treated NB4 cells than that of control group respectively, and 3.62, 2.49, 2.58, 4.27 and 1.94 folds higher in AS2O3 treated NB4 cells than that of control group respectively), except for miR-15b, the expression levels of miR-16, miR-107, miR-223 and miR-342 in ATRA treated group was significantly higher than that in As2O3 treated group. The relative expression levels of miR-15b, miR-16, miR-107, miR-181a, miR-223 and miR-342 were 0.4137, 0.6367, 0.1260, 0.0522, 0.6611, 0.0280 in APL CR group, and 0.0751, 0.2022, 0.0425, 0.3064, 0.1733, 0.0090 in newly diagnosed APL group, respectively. The expression level of miR-15b, miR-16, miR-107, miR-223 and miR-342 in APL CR group were significantly upregulated compared with that of newly diagnosed APL groups (P < 0.05), while the expression level of miR-181a was significantly downregulated (P < 0.05).
  
  
  CONCLUSIONS
  Specific expression of microRNA profiles is a key contributing factor in the differentiation of APL.
authors.affiliation: Fujian Institute of Hematology, Key Laboratory of Hematology, Fujian Province, Union Hospital, Fujian Medical University, Fuzhou 350001, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.forename: Xian-fang
authors.initials: XF
authors.lastname: Li
authors.forename: Jing-hui
authors.initials: JH
authors.lastname: Yang
authors.forename: Xiao-ying
authors.initials: XY
authors.lastname: Liao
authors.forename: Yuan-zhong
authors.initials: YZ
authors.lastname: Chen
mesh_terms: D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D001152:Arsenicals; D035683:MicroRNAs; D010087:Oxides; D012333:RNA, Messenger; D014212:Tretinoin; D000077237:Arsenic Trioxide