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Thymoquinone-Induced Tristetraprolin Inhibits Tumor Growth and Metastasis through Destabilization of MUC4 mRNA

Tristetraprolin (TTP), a well-characterized AU-rich element (ARE) binding protein, functions as a tumor suppressor gene. The purpose of this study was to investigate whether a bioactive substance derived from a natural medicinal plant affects the induction of TTP and to elucidate its mechanism. We e...

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Autores principales: Lee, Se-Ra, Mun, Jeong-Yeon, Jeong, Mi-So, Lee, Hyun-Hee, Roh, Yun-Gil, Kim, Won-Tae, Kim, Min-Hye, Heo, Jeonghoon, Choi, Yung Hyun, Kim, Su Jin, Cha, Hee-Jae, Jun, Mira, Leem, Sun-Hee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600862/
https://www.ncbi.nlm.nih.gov/pubmed/31141941
http://dx.doi.org/10.3390/ijms20112614
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author Lee, Se-Ra
Mun, Jeong-Yeon
Jeong, Mi-So
Lee, Hyun-Hee
Roh, Yun-Gil
Kim, Won-Tae
Kim, Min-Hye
Heo, Jeonghoon
Choi, Yung Hyun
Kim, Su Jin
Cha, Hee-Jae
Jun, Mira
Leem, Sun-Hee
author_facet Lee, Se-Ra
Mun, Jeong-Yeon
Jeong, Mi-So
Lee, Hyun-Hee
Roh, Yun-Gil
Kim, Won-Tae
Kim, Min-Hye
Heo, Jeonghoon
Choi, Yung Hyun
Kim, Su Jin
Cha, Hee-Jae
Jun, Mira
Leem, Sun-Hee
author_sort Lee, Se-Ra
collection PubMed
description Tristetraprolin (TTP), a well-characterized AU-rich element (ARE) binding protein, functions as a tumor suppressor gene. The purpose of this study was to investigate whether a bioactive substance derived from a natural medicinal plant affects the induction of TTP and to elucidate its mechanism. We examined the effects of natural bioactive materials including Resveratrol (RSV), thymoquinone (TQ) and curcumin on the expression of TTP in cancer cell. TQ derived from a natural plant Nigella sativa increased the expression levels of TTP mRNA and proteins in a dose-dependent manner in gastric and breast cancer cells. TQ-induced TTP increased the instability of MUC4 mRNA by direct binding of TTP to ARE in the 3′UTR of MUC4 mRNA. The induction of TTP by TQ also reduced the proliferation, migration and invasion of cancer cells. The expression of the epithelial-mesenchymal (EMT)-related genes, which were target genes of TTP, was also decreased by the TQ treatment. In the in vivo experiments using mouse melanoma cells, TQ-induced TTP inhibited metastasis of tumor cells. We have found that TQ-induced TTP might inhibit metastasis by reducing tumor cell migration and invasion through destabilization of MUC4 mRNA, which suggest the MUC4 as a novel target to TTP.
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spelling pubmed-66008622019-07-18 Thymoquinone-Induced Tristetraprolin Inhibits Tumor Growth and Metastasis through Destabilization of MUC4 mRNA Lee, Se-Ra Mun, Jeong-Yeon Jeong, Mi-So Lee, Hyun-Hee Roh, Yun-Gil Kim, Won-Tae Kim, Min-Hye Heo, Jeonghoon Choi, Yung Hyun Kim, Su Jin Cha, Hee-Jae Jun, Mira Leem, Sun-Hee Int J Mol Sci Article Tristetraprolin (TTP), a well-characterized AU-rich element (ARE) binding protein, functions as a tumor suppressor gene. The purpose of this study was to investigate whether a bioactive substance derived from a natural medicinal plant affects the induction of TTP and to elucidate its mechanism. We examined the effects of natural bioactive materials including Resveratrol (RSV), thymoquinone (TQ) and curcumin on the expression of TTP in cancer cell. TQ derived from a natural plant Nigella sativa increased the expression levels of TTP mRNA and proteins in a dose-dependent manner in gastric and breast cancer cells. TQ-induced TTP increased the instability of MUC4 mRNA by direct binding of TTP to ARE in the 3′UTR of MUC4 mRNA. The induction of TTP by TQ also reduced the proliferation, migration and invasion of cancer cells. The expression of the epithelial-mesenchymal (EMT)-related genes, which were target genes of TTP, was also decreased by the TQ treatment. In the in vivo experiments using mouse melanoma cells, TQ-induced TTP inhibited metastasis of tumor cells. We have found that TQ-induced TTP might inhibit metastasis by reducing tumor cell migration and invasion through destabilization of MUC4 mRNA, which suggest the MUC4 as a novel target to TTP. MDPI 2019-05-28 /pmc/articles/PMC6600862/ /pubmed/31141941 http://dx.doi.org/10.3390/ijms20112614 Text en © 2019 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/).
spellingShingle Article
Lee, Se-Ra
Mun, Jeong-Yeon
Jeong, Mi-So
Lee, Hyun-Hee
Roh, Yun-Gil
Kim, Won-Tae
Kim, Min-Hye
Heo, Jeonghoon
Choi, Yung Hyun
Kim, Su Jin
Cha, Hee-Jae
Jun, Mira
Leem, Sun-Hee
Thymoquinone-Induced Tristetraprolin Inhibits Tumor Growth and Metastasis through Destabilization of MUC4 mRNA
title Thymoquinone-Induced Tristetraprolin Inhibits Tumor Growth and Metastasis through Destabilization of MUC4 mRNA
title_full Thymoquinone-Induced Tristetraprolin Inhibits Tumor Growth and Metastasis through Destabilization of MUC4 mRNA
title_fullStr Thymoquinone-Induced Tristetraprolin Inhibits Tumor Growth and Metastasis through Destabilization of MUC4 mRNA
title_full_unstemmed Thymoquinone-Induced Tristetraprolin Inhibits Tumor Growth and Metastasis through Destabilization of MUC4 mRNA
title_short Thymoquinone-Induced Tristetraprolin Inhibits Tumor Growth and Metastasis through Destabilization of MUC4 mRNA
title_sort thymoquinone-induced tristetraprolin inhibits tumor growth and metastasis through destabilization of muc4 mrna
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600862/
https://www.ncbi.nlm.nih.gov/pubmed/31141941
http://dx.doi.org/10.3390/ijms20112614
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