RRC ID 62754
Author Wang X, Sun J, Cui M, Zhao F, Ge C, Chen T, Yao M, Li J.
Title Downregulation of FOXP1 Inhibits Cell Proliferation in Hepatocellular Carcinoma by Inducing G1/S Phase Cell Cycle Arrest.
Journal Int J Mol Sci
Abstract Forkhead box P1 (FOXP1) belongs to a family of winged-helix transcription factors that are involved in the processes of cellular proliferation, differentiation, metabolism, and longevity. FOXP1 can affect cell proliferation and migratory ability in hepatocellular carcinoma (HCC) in vitro. However, little is known about the mechanism of FOXP1 in the proliferation of HCC cells. This study aimed to further explore the function of FOXP1 on the proliferation of HCC cells as well as the relevant mechanism involved. Western blot analysis, tumor xenograft models, and flow cytometry analysis were performed to elucidate the function of FOXP1 in the regulation of cell proliferation in human HCC. We observed that silencing FOXP1 significantly suppressed the growth ability of HCC cells both in vitro and in vivo. In addition, knockdown of FOXP1 induced G1/S phase arrest, and the expression of total and phosphorylated Rb (active type) as well as the levels of E2F1 were markedly decreased at 24 h; however, other proteins, including cyclin-dependent kinase (CDK) 4 and 6 and cyclin D1 did not show noticeable changes. In conclusion, downregulation of FOXP1 inhibits cell proliferation in hepatocellular carcinoma by inducing G1/S phase cell cycle arrest, and the decrease in phosphorylated Rb is the main contributor to this G1/S phase arrest.
Volume 17(9)
Published 2016-9-8
DOI 10.3390/ijms17091501
PII ijms17091501
PMID 27618020
PMC PMC5037778
MeSH Carcinoma, Hepatocellular / metabolism* Carcinoma, Hepatocellular / pathology Cell Line, Tumor Cell Proliferation* Cyclin D1 / metabolism Cyclin-Dependent Kinases / metabolism Down-Regulation E2F1 Transcription Factor / metabolism Forkhead Transcription Factors / genetics* Forkhead Transcription Factors / metabolism G1 Phase Cell Cycle Checkpoints* Humans Liver Neoplasms / genetics Liver Neoplasms / metabolism* Liver Neoplasms / pathology Repressor Proteins / genetics* Repressor Proteins / metabolism S Phase Cell Cycle Checkpoints*
IF 4.556
Human and Animal Cells HuH-7