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Authors
Tsuchiya, Hiroyuki Graduate School of Medicine, Tottori University Researchers DB KAKEN
Oura, Seiya Graduate School of Pharmaceutical Sciences, Osaka University
Keywords
retinoids
RAR alpha
TFPI2
MAFB
MAFF
hepatocellular carcinoma
invasion
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.
Publisher
MDPI
Content Type
Journal Article
Link
ISSN
14220067
Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Current Journal Title
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume
19
Issue
5
Published Date
2018-05
Publisher-DOI
Rights
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Citation
Tsuchiya Hiroyuki, Oura Seiya. Involvement of MAFB and MAFF in Retinoid-Mediated Suppression of Hepatocellular Carcinoma Invasion. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2018. 19(5). doi:10.3390/ijms19051450
Department
Faculty of Medicine/Graduate School of Medical Sciences/University Hospital
Language
English
Web of Science Key ut
WOS:000435297000186