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*
Resource
Human and Animal Cells HuH-7