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.
Journal Int J Hematol
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
Cord blood stem cells for research