title: The 5' flanking region of miR-378 is hypomethylated in acute myeloid leukemia.
abstract: BACKGROUND
  Aberrant expression of miR-378 has been observed in various malignancies including acute myeloid leukemia (AML). However, the mechanism regulating of miR-378 expression remains unknown. This study was aimed to investigate miR-378 methylation and to explore its clinical significance in AML.
  
  
  METHODS
  Methylation status of miR-378 5'-flanking region was investigated by real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite-sequencing PCR (BSP). The expression of miR-378 was evaluated by real-time quantitative PCR (RQ-PCR). The correlation between expression of miR-378 and 5'-flanking region methylation was analyzed using 5-aza-2'-deoxycytidine (5-aza-dC) treatment.
  
  
  RESULTS
  miR-378 5'-flanking region was significantly hypomethylated in AML patients compared to controls (median 0.109 vs. 0.058) (P=0.048). miR-378 expression was correlated with miR-378 5'-flanking region in leukemic cell line treated with 5-aza-dC, but not in AML patients. The level of miR-378 hypomethylation significantly increased in M2 subtype compared to other subtypes. Moreover, patients with t(8;21) harbored the highest level of miR-378 hypomethylation. However, there was no significant difference in overall survival between patients with high and low miR-378 hypomethylation. The association of miR-378 expression with methylation was not observed in AML patients, but miR-378 expression in THP-1 line was increased while methylation status of miR-378 5-flanking region was decreased after 5-aza-dC treatment.
  
  
  CONCLUSIONS
  Our findings suggest that miR-378 is reactivated by demethylation after 5-aza-dC treatment. 5'-flanking region of miR-378 is hypomethylated in AML especially in those with t(8;21).
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Zhu
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Xiang-Mei
authors.initials: XM
authors.lastname: Wen
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Hong
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Jia-Yu
authors.initials: JY
authors.lastname: Yin
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Ji-Chun
authors.initials: JC
authors.lastname: Ma
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Lin
authors.affiliation: Laboratory Center, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Zhao-Qun
authors.initials: ZQ
authors.lastname: Deng
authors.affiliation: Department of Hematology, Affiliated People's Hospital of Jiangsu University Zhenjiang, Jiangsu, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qian
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D000077209:Decitabine; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; C526012:MIRN378 microRNA, human; D035683:MicroRNAs; D000077209:Decitabine; D001374:Azacitidine
keywords: 5-aza-dC; acute myeloid leukemia; hypomethylation; miR-378