Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica

Acta Academiae Medicinae Sinica ›› 2018, Vol. 40 ›› Issue (3): 308-314.doi: 10.3881/j.issn.1000-503X.2018.03.002

• Original Articles • Previous Articles     Next Articles

Methyltransferase-like 3 Promotes the Proliferation of Acute Myeloid Leukemia Cells by Regulating N6-methyladenosine Levels of MYC

WANG Xiaoshuang,HE Jinrong,YU Shan,YU Jia()   

  1. State Key Lab of Medical Molecular Biology,Department of Biochemistry,Institute of Basic Medical Sciences,CAMS and PUMC,Beijing 100005,China
  • Received:2018-03-20 Online:2018-06-30 Published:2018-07-05
  • Supported by:
    Supported by the CAMS Innovation Fund for Medical Sciences(2017-I2M-3-009)

Abstract:

Objective To investigate the role of methyltransferase-like 3(METTL3) in the proliferation of acute myeloid leukemia (AML) cells and its mechanism.Methods METTL3 expression in AML patients was analyzed in Gene Expression Omnibus data files. METTL3 expression was inhibited by lentivirus-mediated gene transduction in MOLM13 cells,after which cell proliferation was analyzed by cell counting kit-8,N6-methyladenosine (m6A) levels of total mRNA was analyzed by ELISA,specific m6A on MYC was analyzed by gene-specific m6A RNA immunoprecipitation,and MYC expression was analyzed by RT-qPCR and Western blot analysis.Results METTL3 level was slightly increased in AML-M5 patients,and its expression was significantly higher in immature cells than in mature monocytes (t=4.504,P=0.0098). METTL3 knock-down significantly suppressed cell proliferation (P<0.001),reduced m6A level of total mRNA (t=3.606,P=0.042) and specific m6A level on MYC mRNA (P<0.01),and suppressed MYC expression (P<0.01).Conclusion METTL3 acts as an oncogene in MOLM13 cells by upregulating MYC expression.

Key words: methyltransferase-like 3, N6-methyladenosine, acute myeloid leukemia, proliferation, MYC

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