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Inactivation of Stat3 and crosstalk of miRNA155-5p and FOXO3a contribute to the induction of IGFBP1 expression by beta-elemene in human lung cancer

β-Elemene, an active component of natural plants, has been shown to exhibit anticancer properties. However, the detailed mechanism underlying these effects has yet to be determined. In this study, we show that β-elemene inhibits the growth of lung cancer cells. Mechanistically, we found that β-eleme...

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Autores principales: Zheng, Fang, Tang, Qing, Zheng, Xiao-hua, Wu, JingJing, Huang, HaiDing, Zhang, Haibo, Hann, Swei Sunny
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135838/
https://www.ncbi.nlm.nih.gov/pubmed/30209296
http://dx.doi.org/10.1038/s12276-018-0146-6
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author Zheng, Fang
Tang, Qing
Zheng, Xiao-hua
Wu, JingJing
Huang, HaiDing
Zhang, Haibo
Hann, Swei Sunny
author_facet Zheng, Fang
Tang, Qing
Zheng, Xiao-hua
Wu, JingJing
Huang, HaiDing
Zhang, Haibo
Hann, Swei Sunny
author_sort Zheng, Fang
collection PubMed
description β-Elemene, an active component of natural plants, has been shown to exhibit anticancer properties. However, the detailed mechanism underlying these effects has yet to be determined. In this study, we show that β-elemene inhibits the growth of lung cancer cells. Mechanistically, we found that β-elemene decreased the phosphorylation of signal transducer and activator of transcription 3 (Stat3) and miRNA155-5p mRNA but induced the protein expression of human forkhead box class O (FOXO)3a; the latter two were abrogated in cells with overexpressed Stat3. Notably, miRNA155-5p mimics reduced FOXO3a luciferase reporter activity in the 3-UTR region and protein expression, whereas overexpressed FOXO3a countered the reduction of the miRNA155-5p levels by β-elemene. Moreover, β-elemene increased the mRNA and protein expression levels as well as promoter activity of insulin-like growth factor-binding protein 1 (IGFBP1); this finding was not observed in cells with a silenced FOXO3a gene and miRNA155-5p mimics. Finally, silencing of IGFBP1 blocked β-elemene-inhibited cell growth. Similar findings were observed in vivo. In summary, our results indicate that β-elemene increases IGFBP1 gene expression via inactivation of Stat3 followed by a reciprocal interaction between miRNA155-5p and FOXO3a. This effect leads to inhibition of human lung cancer cell growth. These findings reveal a novel molecular mechanism underlying the inhibitory effects of β-elemene on lung cancer cells.
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spelling pubmed-61358382018-09-18 Inactivation of Stat3 and crosstalk of miRNA155-5p and FOXO3a contribute to the induction of IGFBP1 expression by beta-elemene in human lung cancer Zheng, Fang Tang, Qing Zheng, Xiao-hua Wu, JingJing Huang, HaiDing Zhang, Haibo Hann, Swei Sunny Exp Mol Med Article β-Elemene, an active component of natural plants, has been shown to exhibit anticancer properties. However, the detailed mechanism underlying these effects has yet to be determined. In this study, we show that β-elemene inhibits the growth of lung cancer cells. Mechanistically, we found that β-elemene decreased the phosphorylation of signal transducer and activator of transcription 3 (Stat3) and miRNA155-5p mRNA but induced the protein expression of human forkhead box class O (FOXO)3a; the latter two were abrogated in cells with overexpressed Stat3. Notably, miRNA155-5p mimics reduced FOXO3a luciferase reporter activity in the 3-UTR region and protein expression, whereas overexpressed FOXO3a countered the reduction of the miRNA155-5p levels by β-elemene. Moreover, β-elemene increased the mRNA and protein expression levels as well as promoter activity of insulin-like growth factor-binding protein 1 (IGFBP1); this finding was not observed in cells with a silenced FOXO3a gene and miRNA155-5p mimics. Finally, silencing of IGFBP1 blocked β-elemene-inhibited cell growth. Similar findings were observed in vivo. In summary, our results indicate that β-elemene increases IGFBP1 gene expression via inactivation of Stat3 followed by a reciprocal interaction between miRNA155-5p and FOXO3a. This effect leads to inhibition of human lung cancer cell growth. These findings reveal a novel molecular mechanism underlying the inhibitory effects of β-elemene on lung cancer cells. Nature Publishing Group UK 2018-09-12 /pmc/articles/PMC6135838/ /pubmed/30209296 http://dx.doi.org/10.1038/s12276-018-0146-6 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zheng, Fang
Tang, Qing
Zheng, Xiao-hua
Wu, JingJing
Huang, HaiDing
Zhang, Haibo
Hann, Swei Sunny
Inactivation of Stat3 and crosstalk of miRNA155-5p and FOXO3a contribute to the induction of IGFBP1 expression by beta-elemene in human lung cancer
title Inactivation of Stat3 and crosstalk of miRNA155-5p and FOXO3a contribute to the induction of IGFBP1 expression by beta-elemene in human lung cancer
title_full Inactivation of Stat3 and crosstalk of miRNA155-5p and FOXO3a contribute to the induction of IGFBP1 expression by beta-elemene in human lung cancer
title_fullStr Inactivation of Stat3 and crosstalk of miRNA155-5p and FOXO3a contribute to the induction of IGFBP1 expression by beta-elemene in human lung cancer
title_full_unstemmed Inactivation of Stat3 and crosstalk of miRNA155-5p and FOXO3a contribute to the induction of IGFBP1 expression by beta-elemene in human lung cancer
title_short Inactivation of Stat3 and crosstalk of miRNA155-5p and FOXO3a contribute to the induction of IGFBP1 expression by beta-elemene in human lung cancer
title_sort inactivation of stat3 and crosstalk of mirna155-5p and foxo3a contribute to the induction of igfbp1 expression by beta-elemene in human lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135838/
https://www.ncbi.nlm.nih.gov/pubmed/30209296
http://dx.doi.org/10.1038/s12276-018-0146-6
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