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Hinokitiol up-regulates miR-494-3p to suppress BMI1 expression and inhibits self-renewal of breast cancer stem/progenitor cells

Hinokitiol (β-thujaplicin) is a tropolone-related compound that has anti-microbe, anti-inflammation, and anti-tumor effects. Cancer stem/progenitor cells (CSCs) are a subpopulation of cancer cells with tumor initiation, chemoresistant, and metastatic properties and have been considered the important...

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Autores principales: Chen, Shih-Ming, Wang, Bing-Yen, Lee, Che-Hsin, Lee, Hsueh-Te, Li, Jung-Jung, Hong, Guan-Ci, Hung, Yu-Chieh, Chien, Peng-Ju, Chang, Che-Ying, Hsu, Li-Sung, Chang, Wen-Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652685/
https://www.ncbi.nlm.nih.gov/pubmed/29100291
http://dx.doi.org/10.18632/oncotarget.18648
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author Chen, Shih-Ming
Wang, Bing-Yen
Lee, Che-Hsin
Lee, Hsueh-Te
Li, Jung-Jung
Hong, Guan-Ci
Hung, Yu-Chieh
Chien, Peng-Ju
Chang, Che-Ying
Hsu, Li-Sung
Chang, Wen-Wei
author_facet Chen, Shih-Ming
Wang, Bing-Yen
Lee, Che-Hsin
Lee, Hsueh-Te
Li, Jung-Jung
Hong, Guan-Ci
Hung, Yu-Chieh
Chien, Peng-Ju
Chang, Che-Ying
Hsu, Li-Sung
Chang, Wen-Wei
author_sort Chen, Shih-Ming
collection PubMed
description Hinokitiol (β-thujaplicin) is a tropolone-related compound that has anti-microbe, anti-inflammation, and anti-tumor effects. Cancer stem/progenitor cells (CSCs) are a subpopulation of cancer cells with tumor initiation, chemoresistant, and metastatic properties and have been considered the important therapeutic target in future cancer therapy. Previous studies reported that hinokitiol exhibits an anti-cancer activity against murine tumor cells through the induction of autophagy. The current research revealed that hinokitiol suppressed the self-renewal capabilities of human breast CSCs (BCSCs) and inhibited the expression of BMI1 at protein level without suppressing its mRNA. Treatment of hinokitiol in mammospheres induced the expression of miR-494-3p and inhibition of miR-494-3p expression in BCSCs. This treatment abolished the suppressive effects of hinokitiol in mammosphere formation and BMI1 expression. BMI1 is a target of miR-494-3p by luciferase-based 3′UTR reporter assay. Overexpression of miR-494-3p in BCSCs caused the down-regulation of BMI1 protein, inhibition of mammosphere forming capability, and suppression of their tumorigenicity. Moreover, miR-494-3p expression was significantly and inversely correlated with patient survival in two independent public database sets. Furthermore, treatment of hinokitiol in vivo suppressed the growth of xenograft human breast tumors as well as the expression of BMI1 and ALDH1A1 in xenograft tumors. In conclusion, these data suggest that hinokitiol targets BCSCs through the miR-494-3p-mediated down-modulation of BMI1 expression.
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spelling pubmed-56526852017-11-02 Hinokitiol up-regulates miR-494-3p to suppress BMI1 expression and inhibits self-renewal of breast cancer stem/progenitor cells Chen, Shih-Ming Wang, Bing-Yen Lee, Che-Hsin Lee, Hsueh-Te Li, Jung-Jung Hong, Guan-Ci Hung, Yu-Chieh Chien, Peng-Ju Chang, Che-Ying Hsu, Li-Sung Chang, Wen-Wei Oncotarget Research Paper Hinokitiol (β-thujaplicin) is a tropolone-related compound that has anti-microbe, anti-inflammation, and anti-tumor effects. Cancer stem/progenitor cells (CSCs) are a subpopulation of cancer cells with tumor initiation, chemoresistant, and metastatic properties and have been considered the important therapeutic target in future cancer therapy. Previous studies reported that hinokitiol exhibits an anti-cancer activity against murine tumor cells through the induction of autophagy. The current research revealed that hinokitiol suppressed the self-renewal capabilities of human breast CSCs (BCSCs) and inhibited the expression of BMI1 at protein level without suppressing its mRNA. Treatment of hinokitiol in mammospheres induced the expression of miR-494-3p and inhibition of miR-494-3p expression in BCSCs. This treatment abolished the suppressive effects of hinokitiol in mammosphere formation and BMI1 expression. BMI1 is a target of miR-494-3p by luciferase-based 3′UTR reporter assay. Overexpression of miR-494-3p in BCSCs caused the down-regulation of BMI1 protein, inhibition of mammosphere forming capability, and suppression of their tumorigenicity. Moreover, miR-494-3p expression was significantly and inversely correlated with patient survival in two independent public database sets. Furthermore, treatment of hinokitiol in vivo suppressed the growth of xenograft human breast tumors as well as the expression of BMI1 and ALDH1A1 in xenograft tumors. In conclusion, these data suggest that hinokitiol targets BCSCs through the miR-494-3p-mediated down-modulation of BMI1 expression. Impact Journals LLC 2017-06-27 /pmc/articles/PMC5652685/ /pubmed/29100291 http://dx.doi.org/10.18632/oncotarget.18648 Text en Copyright: © 2017 Chen et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Chen, Shih-Ming
Wang, Bing-Yen
Lee, Che-Hsin
Lee, Hsueh-Te
Li, Jung-Jung
Hong, Guan-Ci
Hung, Yu-Chieh
Chien, Peng-Ju
Chang, Che-Ying
Hsu, Li-Sung
Chang, Wen-Wei
Hinokitiol up-regulates miR-494-3p to suppress BMI1 expression and inhibits self-renewal of breast cancer stem/progenitor cells
title Hinokitiol up-regulates miR-494-3p to suppress BMI1 expression and inhibits self-renewal of breast cancer stem/progenitor cells
title_full Hinokitiol up-regulates miR-494-3p to suppress BMI1 expression and inhibits self-renewal of breast cancer stem/progenitor cells
title_fullStr Hinokitiol up-regulates miR-494-3p to suppress BMI1 expression and inhibits self-renewal of breast cancer stem/progenitor cells
title_full_unstemmed Hinokitiol up-regulates miR-494-3p to suppress BMI1 expression and inhibits self-renewal of breast cancer stem/progenitor cells
title_short Hinokitiol up-regulates miR-494-3p to suppress BMI1 expression and inhibits self-renewal of breast cancer stem/progenitor cells
title_sort hinokitiol up-regulates mir-494-3p to suppress bmi1 expression and inhibits self-renewal of breast cancer stem/progenitor cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652685/
https://www.ncbi.nlm.nih.gov/pubmed/29100291
http://dx.doi.org/10.18632/oncotarget.18648
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