Abstract
ZBTB3 belongs to the Zinc finger and BTB/POZ domain containing transcription factor family; however, its biological role has rarely been studied. We demonstrate for the first time, to our knowledge, that ZBTB3 is an essential factor for cancer cell growth via the regulation of the ROS detoxification pathway. Suppression of ZBTB3 using two different short hairpin RNAs in human melanoma, lung carcinoma, and breast carcinoma results in diminished cell growth. In addition, we found that suppression of ZBTB3 activates a caspase cascade, including caspase-9, -3, and PARP leading to cellular apoptosis, resulting from failed ROS detoxification. We identified that ZBTB3 plays an important role in the gene expression of ROS detoxification enzymes. Our results reveal that ZBTB3 may play a critical role in cancer cell growth via the ROS detoxification system. Therefore, therapeutic strategies that target ZBTB3 could be used in selective cancer treatments.
MeSH Terms
Apoptosis
Caspase 3/metabolism
Caspase 9/metabolism
Cell Line, Tumor
Cell Proliferation
DNA-Binding Proteins/antagonists & inhibitors,genetics,metabolism
HEK293 Cells
Humans
Poly(ADP-ribose) Polymerases/metabolism
RNA Interference
RNA, Small Interfering/metabolism
Reactive Oxygen Species/metabolism
Repressor Proteins/antagonists & inhibitors,genetics,metabolism
Chemicals
DNA-Binding Proteins
RNA, Small Interfering
Reactive Oxygen Species
Repressor Proteins
ZBTB3 protein, human
Poly(ADP-ribose) Polymerases
Caspase 3
Caspase 9
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Lim Ji-Hong
Department of Biomedical Chemistry, College of Biomedical and Health Science, Konkuk University, Chungju 380-701, Korea.
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