SLIT2 promoter hypermethylation-mediated SLIT2-IT1/miR-218 repression drives leukemogenesis and predicts adverse prognosis in myelodysplastic neoplasm View Full Text


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Article Info

DATE

2022-07-29

AUTHORS

Ting-juan Zhang, Zi-jun Xu, Xiang-mei Wen, Yu Gu, Ji-chun Ma, Qian Yuan, Jiang Lin, Jing-dong Zhou, Jun Qian

ABSTRACT

Epigenetic modifications have been found to play crucial roles in myelodysplastic neoplasm (MDS) progression. Previously, we investigated genome-wide DNA methylation alterations during MDS evolution to acute myeloid leukemia (AML) by next-generation sequencing (NGS). Herein, we further determined the role and clinical implications of an evident methylation change in CpG islands at the SLIT2 promoter identified by NGS. First, increased SLIT2 promoter methylation was validated in 11 paired MDS/AML patients during disease evolution. Additionally, SLIT2 promoter methylation was markedly increased in MDS/AML patients compared with controls and was correlated with poor clinical phenotype and outcome. Interestingly, SLIT2 expression was particularly upregulated in AML patients and was not correlated with SLIT2 promoter methylation. However, the SLIT2-embedded genes SLIT2-IT1 and miR-218 were downregulated in AML patients, which was negatively associated with SLIT2 promoter methylation and further validated by demethylation studies. Functionally, SLIT2-IT1/miR-218 overexpression exhibited antileukemic effects by affecting cell proliferation, apoptosis and colony formation in vitro and in vivo. Mechanistically, SLIT2-IT1 may function as a competing endogenous RNA by sponging miR-3156-3p to regulate BMF expression, whereas miR-218 may directly target HOXA1 in MDS progression. In summary, our findings demonstrate that SLIT2 promoter hypermethylation is associated with disease evolution in MDS and predicts poor prognoses in both MDS and AML. Epigenetic inactivation of SLIT2-IT1/miR-218 by SLIT2 promoter hypermethylation could be a promising therapeutic target in MDS. More... »

PAGES

1-11

References to SciGraph publications

  • 2012-02-13. Protein L: a novel reagent for the detection of Chimeric Antigen Receptor (CAR) expression by flow cytometry in JOURNAL OF TRANSLATIONAL MEDICINE
  • 2012-10-01. Acute myeloid leukemia with translocation (8;16)(p11;p13) and MYST3-CREBBP rearrangement harbors a distinctive microRNA signature targeting RET proto-oncogene in LEUKEMIA
  • 2015-11-26. Whole-exome and targeted sequencing identify ROBO1 and ROBO2 mutations as progression-related drivers in myelodysplastic syndromes in NATURE COMMUNICATIONS
  • 2019-02-09. Low Expression and Promoter Hypermethylation of the Tumour Suppressor SLIT2, are Associated with Adverse Patient Outcomes in Diffuse Large B Cell Lymphoma in PATHOLOGY & ONCOLOGY RESEARCH
  • 2018-07-05. Identification and validation of SRY-box containing gene family member SOX30 methylation as a prognostic and predictive biomarker in myeloid malignancies in CLINICAL EPIGENETICS
  • 2006-05-15. Promoter hypermethylation-mediated inactivation of multiple Slit-Robo pathway genes in cervical cancer progression in MOLECULAR CANCER
  • 2020-11-20. Genome-wide methylation sequencing identifies progression-related epigenetic drivers in myelodysplastic syndromes in CELL DEATH & DISEASE
  • 2022-06-22. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms in LEUKEMIA
  • 2019-02-28. The Expression of the SLIT–ROBO Family in Adult Patients with Acute Myeloid Leukemia in ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS
  • 2020-09-30. Tumoural activation of TLR3–SLIT2 axis in endothelium drives metastasis in NATURE
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    17 schema:description Epigenetic modifications have been found to play crucial roles in myelodysplastic neoplasm (MDS) progression. Previously, we investigated genome-wide DNA methylation alterations during MDS evolution to acute myeloid leukemia (AML) by next-generation sequencing (NGS). Herein, we further determined the role and clinical implications of an evident methylation change in CpG islands at the SLIT2 promoter identified by NGS. First, increased SLIT2 promoter methylation was validated in 11 paired MDS/AML patients during disease evolution. Additionally, SLIT2 promoter methylation was markedly increased in MDS/AML patients compared with controls and was correlated with poor clinical phenotype and outcome. Interestingly, SLIT2 expression was particularly upregulated in AML patients and was not correlated with SLIT2 promoter methylation. However, the SLIT2-embedded genes SLIT2-IT1 and miR-218 were downregulated in AML patients, which was negatively associated with SLIT2 promoter methylation and further validated by demethylation studies. Functionally, SLIT2-IT1/miR-218 overexpression exhibited antileukemic effects by affecting cell proliferation, apoptosis and colony formation in vitro and in vivo. Mechanistically, SLIT2-IT1 may function as a competing endogenous RNA by sponging miR-3156-3p to regulate BMF expression, whereas miR-218 may directly target HOXA1 in MDS progression. In summary, our findings demonstrate that SLIT2 promoter hypermethylation is associated with disease evolution in MDS and predicts poor prognoses in both MDS and AML. Epigenetic inactivation of SLIT2-IT1/miR-218 by SLIT2 promoter hypermethylation could be a promising therapeutic target in MDS.
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    21 schema:keywords AML patients
    22 Bmf expression
    23 CpG islands
    24 DNA methylation alterations
    25 HOXA1
    26 Herein
    27 MDS
    28 MDS evolution
    29 MDS progression
    30 MDS/AML patients
    31 Mechanistically
    32 RNA
    33 SLIT2
    34 SLIT2 expression
    35 acute myeloid leukemia
    36 adverse prognosis
    37 alterations
    38 antileukemic effect
    39 apoptosis
    40 cell proliferation
    41 changes
    42 clinical implications
    43 clinical phenotype
    44 colony formation
    45 control
    46 crucial role
    47 demethylation studies
    48 disease evolution
    49 effect
    50 endogenous RNA
    51 epigenetic inactivation
    52 epigenetic modifications
    53 evolution
    54 expression
    55 findings
    56 formation
    57 genome-wide DNA methylation alterations
    58 hypermethylation
    59 implications
    60 inactivation
    61 islands
    62 leukemia
    63 leukemogenesis
    64 methylation
    65 methylation alterations
    66 methylation changes
    67 miR
    68 miR-218
    69 modification
    70 myelodysplastic neoplasms
    71 myeloid leukemia
    72 neoplasm progression
    73 neoplasms
    74 next-generation sequencing
    75 outcomes
    76 overexpression
    77 patients
    78 phenotype
    79 poor prognosis
    80 prognosis
    81 progression
    82 proliferation
    83 promising therapeutic target
    84 promoter
    85 promoter hypermethylation
    86 promoter methylation
    87 repression
    88 role
    89 sequencing
    90 study
    91 summary
    92 target
    93 therapeutic target
    94 vitro
    95 vivo
    96 schema:name SLIT2 promoter hypermethylation-mediated SLIT2-IT1/miR-218 repression drives leukemogenesis and predicts adverse prognosis in myelodysplastic neoplasm
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