RRC ID |
60702
|
Author |
Thanh Nha Uyen L, Amano Y, Al-Kzayer LFY, Kubota N, Kobayashi J, Nakazawa Y, Koike K, Sakashita K.
|
Title |
PCDH17 functions as a common tumor suppressor gene in acute leukemia and its transcriptional downregulation is mediated primarily by aberrant histone acetylation, not DNA methylation.
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Journal |
Int J Hematol
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Abstract |
We recently reported that methylation of PCDH17 gene is found in 30% of children with B-cell precursor acute lymphoblastic leukemia (ALL), and is significantly correlated to event-free or overall survival. We here evaluated PCDH17 mRNA expression in pediatric acute myeloid leukemia (AML) and ALL. PCDH17 mRNA expression levels in children with ALL/AML were lower than those in healthy counterparts. We next elucidated the mechanism underlying down-regulation of PCDH17 mRNA, using myeloid and lymphoid leukemic cell lines. Treatment with the histone deacetylase inhibitor trichostatin A (TSA) resulted in restoration of PCDH17 mRNA expression and growth inhibition in K562, HL60, REH, and RCH-ACV cell lines. Upregulation of PCDH17 mRNA expression resulted from histone H3 acetylation. Knockdown of the PCDH17 gene, caused by transduction of PCDH17-targeted shRNA, significantly enhanced the proliferation of KU812 cells. Meanwhile, overexpression of PCDH17 via retroviral-particle transfection substantially inhibited the growth of Kasumi1 cells. The fold-increase in PCDH17 mRNA expression mediated by 5-azacytidine, an inhibitor of DNA methyltransferase, was fundamentally lower than that produced by TSA. In conclusion, our results suggest that PCDH17 gene functions as a common tumor suppressor gene in leukemic cells, and that histone deacetylase inhibitors re-express PCDH17 mRNA to a greater extent than demethylation reagents.
|
Volume |
111(3)
|
Pages |
451-462
|
Published |
2020-3-1
|
DOI |
10.1007/s12185-019-02799-4
|
PII |
10.1007/s12185-019-02799-4
|
PMID |
31865541
|
MeSH |
Acetylation
Acute Disease
Cadherins / genetics
Cadherins / physiology*
Cell Line, Tumor
Cells, Cultured
Child, Preschool
DNA Methylation
Down-Regulation*
Gene Expression
Genes, Tumor Suppressor*
Histones / metabolism*
Humans
Leukemia, Myeloid, Acute / genetics*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Transcription, Genetic*
|
IF |
2.245
|
Times Cited |
0
|
Resource |
Cord blood stem cells for research |
|