Gene silencing of MIR22 in acute lymphoblastic leukaemia involves histone modifications independent of promoter DNA methylation

Xiaoqing Li, Jun Liu, Rui Zhou, Shi Huang, Shiang Huang, Xian-Ming Chen

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Aberrant epigenetic regulation has recently been implicated in the downregulation of tumour suppressor microRNAs (miRNAs). Histone modification and DNA methylation can have different roles in gene silencing in cancer. To investigate whether histone modifications would contribute to the dysregulation of miRNAs in acute lymphoblastic leukaemia (ALL), the effect of a histone deacetylase inhibitor, trichostatin A (TSA), on miRNA expression profile was analysed by microarray assay in a precursor B-cell ALL cell line NALM-6. A total of 10 miRNAs were downregulated and 31 were upregulated significantly following TSA treatment. Among TSA-upregulated miRNAs, MIR22 is an extronic miRNA and resides in the second exon of the non-coding transcript MGC14376. Upregulation of MIR22 transcription was found in both NALM-6 cells and primary human ALL malignant cells treated with TSA. Whereas a CpG island was identified within the promoter element of MIR22, no promoter DNA methylation was detected in these cells. In contrast, accumulation of the repressive histone marker H3K27 trimethylation (H3K27triM) was indentified around the transcriptional start point of the gene, which was reduced by TSA treatment. Thus, accumulation of H3K27triM independent of promoter DNA methylation may be a novel epigenetic mechanism for MIR22 silencing in ALL.

Original languageEnglish
Pages (from-to)69-79
Number of pages11
JournalBritish Journal of Haematology
Volume148
Issue number1
DOIs
StatePublished - Jan 2010

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Histone Code
trichostatin A
Gene Silencing
DNA Methylation
MicroRNAs
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Epigenomics
Down-Regulation
Precursor B-Cell Lymphoblastic Leukemia-Lymphoma
CpG Islands
Histone Deacetylase Inhibitors
Histones
Exons
Neoplasms
Up-Regulation
Cell Line

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Gene silencing of MIR22 in acute lymphoblastic leukaemia involves histone modifications independent of promoter DNA methylation. / Li, Xiaoqing; Liu, Jun; Zhou, Rui; Huang, Shi; Huang, Shiang; Chen, Xian-Ming.

In: British Journal of Haematology, Vol. 148, No. 1, 01.2010, p. 69-79.

Research output: Contribution to journalArticle

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