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Int. J. Mol. Sci. 2018, 19(5), 1450; https://doi.org/10.3390/ijms19051450

Involvement of MAFB and MAFF in Retinoid-Mediated Suppression of Hepatocellular Carcinoma Invasion

1
Graduate School of Medicine, Tottori University, Tottori 680-8550, Japan
2
Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan
*
Author to whom correspondence should be addressed.
Received: 19 March 2018 / Revised: 28 April 2018 / Accepted: 10 May 2018 / Published: 13 May 2018
(This article belongs to the Special Issue Molecular Biology of Nuclear Receptors)
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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. View Full-Text
Keywords: retinoids; RARα; TFPI2; MAFB; MAFF; hepatocellular carcinoma; invasion retinoids; RARα; TFPI2; MAFB; MAFF; hepatocellular carcinoma; invasion
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Tsuchiya, H.; Oura, S. Involvement of MAFB and MAFF in Retinoid-Mediated Suppression of Hepatocellular Carcinoma Invasion. Int. J. Mol. Sci. 2018, 19, 1450.

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