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)