RRC ID |
68538
|
Author |
Tsuchiya H, Oura S.
|
Title |
Involvement of MAFB and MAFF in Retinoid-Mediated Suppression of Hepatocellular Carcinoma Invasion.
|
Journal |
Int J Mol Sci
|
Abstract |
Retinoids exert antitumor effects through the retinoic acid receptor α (RARα). In the present study, we sought to identify the factors involved in the RARα-mediated transcriptional regulation of the tumor suppressor gene and the tissue factor pathway inhibitor 2 (TFPI2) in hepatocellular carcinoma (HCC). All-trans-retinoic acid (ATRA) was used in the in vitro experiments. Cell invasiveness was measured using trans-well invasion assay. ATRA significantly increased TFPI2 expression through RARα in a human HCC cell line known as HuH7. TFPI2 was vital in the ATRA-mediated suppression of HuH7 cell invasion. The musculo-aponeurotic fibrosarcoma oncogene homolog B (MAFB) significantly enhanced the activation of the TFPI2 promoter via RARα while MAFF inhibited it. The knockdown of RARα or MAFB counteracted the ATRA-mediated suppression of HuH7 cell invasion while the knockdown of MAFF inhibited the invasion. TFPI2 expression in HCC tissues was significantly downregulated possibly due to the decreased expression of RARβ and MAFB. Patients with HCC expressing low MAFB and high MAFF levels showed the shortest disease-free survival time. These results suggest that MAFB and MAFF play critical roles in the antitumor effects of retinoids by regulating the expression of retinoid target genes such as TFPI2 and can be promising for developing therapies to combat HCC invasion.
|
Volume |
19(5)
|
Published |
2018-5-13
|
DOI |
10.3390/ijms19051450
|
PII |
ijms19051450
|
PMID |
29757260
|
PMC |
PMC5983688
|
MeSH |
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / mortality
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
Cell Movement / genetics
Disease Progression
Gene Expression Regulation, Neoplastic
Glycoproteins / genetics
Glycoproteins / metabolism
Humans
Kaplan-Meier Estimate
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Liver Neoplasms / mortality
Liver Neoplasms / pathology
MafB Transcription Factor / genetics*
MafB Transcription Factor / metabolism
MafF Transcription Factor / genetics*
MafF Transcription Factor / metabolism
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Prognosis
Promoter Regions, Genetic
Retinoic Acid Receptor alpha / metabolism
Retinoids / metabolism*
Retinoids / pharmacology
Transcription, Genetic
Tumor Cells, Cultured
|
Resource |
Human and Animal Cells |
KMST-6(RCB1955)
Hep G2(RCB1648)
HuH-7(RCB1366) |