RRC ID |
72570
|
Author |
Sun J, Wang B, Liu Y, Zhang L, Ma A, Yang Z, Ji Y, Liu Y.
|
Title |
Transcription factor KLF9 suppresses the growth of hepatocellular carcinoma cells in vivo and positively regulates p53 expression.
|
Journal |
Cancer Lett
|
Abstract |
Krüppel-like factor 9 (KLF9) is known to be a tumor suppressor gene in colorectal tumors and glioblastoma; however, the functional status and significance of KLF9 in hepatocellular carcinoma (HCC) is unclear. We report here that KLF9 is downregulated in HCC tissues. Restoration of KLF9 significantly inhibited growth and caused apoptosis in SK-Hep1 and HepG2 cells. We found that KLF9 positively regulated p53 levels by directly binding to GC boxes within the proximal region of the p53 promoter. Moreover, in the presence of cycloheximide, KLF9 significantly increased p53 stability in HCC cells. Remarkably, ectopic expression of KLF9 was sufficient to delay the onset of tumors and to promote regression of the established tumors in vivo, suggesting that KLF9 plays a critical role in HCC development and that pharmacological or genetic activation of KLF9 may have potential in the treatment of HCC.
|
Volume |
355(1)
|
Pages |
25-33
|
Published |
2014-12-1
|
DOI |
10.1016/j.canlet.2014.09.022
|
PII |
S0304-3835(14)00534-5
|
PMID |
25242357
|
MeSH |
Animals
Apoptosis
Binding Sites
Carcinoma, Hepatocellular / genetics
Carcinoma, Hepatocellular / metabolism*
Carcinoma, Hepatocellular / pathology
Cell Proliferation*
Gene Expression Regulation, Neoplastic
Hep G2 Cells
Humans
Kruppel-Like Transcription Factors / genetics
Kruppel-Like Transcription Factors / metabolism*
Liver Neoplasms / genetics
Liver Neoplasms / metabolism*
Liver Neoplasms / pathology
Male
Mice, Inbred BALB C
Mice, Nude
Promoter Regions, Genetic
Protein Stability
Signal Transduction
Time Factors
Transcription, Genetic
Transfection
Tumor Suppressor Protein p53 / genetics
Tumor Suppressor Protein p53 / metabolism*
|
IF |
7.36
|
Resource |
Human and Animal Cells |
HuH-7 |