Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Target Concepts:
Gene/Protein
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Query: UMLS:C0026764 (
multiple myeloma
)
36,148
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The KRAB-zinc-finger protein
ZNF545
was recently identified as a potential suppressor gene in several tumors. However, the regulatory mechanisms of
ZNF545
in tumorigenesis remain unclear. In this study, we investigated the expression and roles of
ZNF545
in
multiple myeloma
(MM).
ZNF545
was frequently downregulated in MM tissues compared with non-tumor bone marrow tissues.
ZNF545
expression was silenced by promoter methylation in MM cell lines, and could be restored by demethylation treatment.
ZNF545
methylation was detected in 28.3% of MM tissues, compared with 4.3% of normal bone marrow tissues.
ZNF545
transcriptionally activated the p53 signaling pathway but had no effect on Akt in MM, whereas ectopic expression of
ZNF545
in silenced cells suppressed their proliferation and induced apoptosis. We therefore identified
ZNF545
as a novel tumor suppressor inhibiting tumor growth through activation of the p53 pathway in MM. Moreover, tumor-specific methylation of
ZNF545
may represent an epigenetic biomarker for MM diagnosis, and a potential target for specific therapy.
...
PMID:Epigenetic identification of ZNF545 as a functional tumor suppressor in multiple myeloma via activation of p53 signaling pathway. 2715 Jun 32
This study aimed to investigate the mechanism underlying the inhibitory effect of tumor suppressor gene miR-186 and
zinc finger protein 545
(
ZNF545
) on the proliferation of
multiple myeloma
(MM) cells. CD138 magnetic beads were used to isolate different types of
myeloma
cell lines (KM3, U266, RPMI-8226, and H929), which were then infected by lentivirus carrying the miR-186 gene. Using uninfected
myeloma
cells as the control, MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide] assay was performed to calculate the rate of cell proliferation at different time points. In addition, the correlation between the expression of Jagged 1 and miR-186 was analyzed by real-time Polymerase Chain Reaction (PCR). Furthermore, the effect of 5-Aza-2-deoxycytidine and acetylase inhibitor Trichomycin A (TSA) on the expression of
ZNF545
and proliferation/apoptosis of MM cells was investigated using Reverse Transcription-Polymerase Chain Reaction (RT-PCR), Western blotting (WB), MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] cell proliferation assay, and Annexin V-FITC/PI staining. Compared with the control group, the proliferation of miR-186-overexpressing U266 and RPMI-8226 cells was significantly decreased. In cell cloning experiments, miR-186 decreased the number of U266 and RPMI-8226 clones while reducing the protein expression of Jagged 1. The expression level of
ZNF545
in
myeloma
patients was also reduced to some extent.
ZNF545
protein also promoted the apoptosis of
myeloma
cells. By inhibiting the proliferation of
myeloma
cells, miR-186 gene and ZNF protein may be used as tumor suppressors in the treatment of
myeloma
.
...
PMID:The role of MIR-186 and ZNF545 in inhibiting the proliferation of multiple myeloma cells. 3116 10
