The miR-204-3p-targeted IGFBP2 pathway is involved in xanthohumol-induced glioma cell apoptotic death

Peng Hsu Chen, Cheng Kuei Chang, Chwen Ming Shih, Chia Hsiung Cheng, Cheng Wei Lin, Chin Cheng Lee, Ann Jeng Liu, Kuo Hao Ho, Ku Chung Chen

研究成果: 雜誌貢獻文章

25 引文 (Scopus)

摘要

Xanthohumol (XN), a prenylated chalcone extracted from hop plant Humulus lupulus L. (Cannabaceae), has potential for cancer therapy, including gliomas. Micro (mi)RNAs are small noncoding RNAs that control gene expression. Several miRNAs have been identified to participate in regulating glioma development. However, no studies have demonstrated whether miRNA is involved in XN cytotoxicity resulting in glioma cell death. This study investigated the effects of XN-mediated miRNA expression in activating apoptotic pathways in glioblastoma U87 MG cells. First, we found that XN significantly reduced cell viability and induced apoptosis via pro-caspase-3/8 cleavage and poly(ADP ribose) polymerase (PARP) degradation. We also identified that pro-caspase-9 cleavage, Bcl2 family expression changes, mitochondrial dysfunction, and intracellular ROS generation also participated in XN-induced glioma cell death. With a microarray analysis, miR-204-3p was identified as the most upregulated miRNA induced by XN cytotoxicity. The extracellular signal-regulated kinase (ERK)/c-Fos pathway was validated to participate in XN-upregulated miR-204-3p expression. With a promoter assay and ChIP analysis, we found that c-Fos dose-dependently bound to the miR-204-3p gene promoter region. Furthermore, miR-204-3p levels decreased in several glioma cell lines compared to astrocytes. Overexpression of miR-204-3p enhanced glioma cell apoptosis. IGFBP2, an upregulated regulator of glioma proliferation, was validated by a TCGA analysis as a direct target gene of miR-204-3p. XN's inhibition of the IGFBP2/AKT/Bcl2 pathway via miR-204-3p targeting played a critical role in mediating glioma cell death. These results emphasized that the XN-mediated miR-204-3p network may provide novel therapeutic strategies for future glioblastoma therapy and drug development.
原文英語
頁(從 - 到)362-375
頁數14
期刊Neuropharmacology
110
DOIs
出版狀態已發佈 - 十一月 1 2016

指紋

Glioma
Cell Death
MicroRNAs
Humulus
Glioblastoma
Cannabaceae
Apoptosis
Chalcone
Small Untranslated RNA
Poly(ADP-ribose) Polymerases
xanthohumol
Caspase 9
Caspase 8
Extracellular Signal-Regulated MAP Kinases
Microarray Analysis
Genetic Promoter Regions
Caspase 3
Astrocytes
Genes
Cell Survival

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

引用此文

The miR-204-3p-targeted IGFBP2 pathway is involved in xanthohumol-induced glioma cell apoptotic death. / Chen, Peng Hsu; Chang, Cheng Kuei; Shih, Chwen Ming; Cheng, Chia Hsiung; Lin, Cheng Wei; Lee, Chin Cheng; Liu, Ann Jeng; Ho, Kuo Hao; Chen, Ku Chung.

於: Neuropharmacology, 卷 110, 01.11.2016, p. 362-375.

研究成果: 雜誌貢獻文章

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title = "The miR-204-3p-targeted IGFBP2 pathway is involved in xanthohumol-induced glioma cell apoptotic death",
abstract = "Xanthohumol (XN), a prenylated chalcone extracted from hop plant Humulus lupulus L. (Cannabaceae), has potential for cancer therapy, including gliomas. Micro (mi)RNAs are small noncoding RNAs that control gene expression. Several miRNAs have been identified to participate in regulating glioma development. However, no studies have demonstrated whether miRNA is involved in XN cytotoxicity resulting in glioma cell death. This study investigated the effects of XN-mediated miRNA expression in activating apoptotic pathways in glioblastoma U87 MG cells. First, we found that XN significantly reduced cell viability and induced apoptosis via pro-caspase-3/8 cleavage and poly(ADP ribose) polymerase (PARP) degradation. We also identified that pro-caspase-9 cleavage, Bcl2 family expression changes, mitochondrial dysfunction, and intracellular ROS generation also participated in XN-induced glioma cell death. With a microarray analysis, miR-204-3p was identified as the most upregulated miRNA induced by XN cytotoxicity. The extracellular signal-regulated kinase (ERK)/c-Fos pathway was validated to participate in XN-upregulated miR-204-3p expression. With a promoter assay and ChIP analysis, we found that c-Fos dose-dependently bound to the miR-204-3p gene promoter region. Furthermore, miR-204-3p levels decreased in several glioma cell lines compared to astrocytes. Overexpression of miR-204-3p enhanced glioma cell apoptosis. IGFBP2, an upregulated regulator of glioma proliferation, was validated by a TCGA analysis as a direct target gene of miR-204-3p. XN's inhibition of the IGFBP2/AKT/Bcl2 pathway via miR-204-3p targeting played a critical role in mediating glioma cell death. These results emphasized that the XN-mediated miR-204-3p network may provide novel therapeutic strategies for future glioblastoma therapy and drug development.",
keywords = "ERK/c-Fos pathway, Glioblastoma, IGFBP2, miR-204-3p, Xanthohumol",
author = "Chen, {Peng Hsu} and Chang, {Cheng Kuei} and Shih, {Chwen Ming} and Cheng, {Chia Hsiung} and Lin, {Cheng Wei} and Lee, {Chin Cheng} and Liu, {Ann Jeng} and Ho, {Kuo Hao} and Chen, {Ku Chung}",
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T1 - The miR-204-3p-targeted IGFBP2 pathway is involved in xanthohumol-induced glioma cell apoptotic death

AU - Chen, Peng Hsu

AU - Chang, Cheng Kuei

AU - Shih, Chwen Ming

AU - Cheng, Chia Hsiung

AU - Lin, Cheng Wei

AU - Lee, Chin Cheng

AU - Liu, Ann Jeng

AU - Ho, Kuo Hao

AU - Chen, Ku Chung

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Xanthohumol (XN), a prenylated chalcone extracted from hop plant Humulus lupulus L. (Cannabaceae), has potential for cancer therapy, including gliomas. Micro (mi)RNAs are small noncoding RNAs that control gene expression. Several miRNAs have been identified to participate in regulating glioma development. However, no studies have demonstrated whether miRNA is involved in XN cytotoxicity resulting in glioma cell death. This study investigated the effects of XN-mediated miRNA expression in activating apoptotic pathways in glioblastoma U87 MG cells. First, we found that XN significantly reduced cell viability and induced apoptosis via pro-caspase-3/8 cleavage and poly(ADP ribose) polymerase (PARP) degradation. We also identified that pro-caspase-9 cleavage, Bcl2 family expression changes, mitochondrial dysfunction, and intracellular ROS generation also participated in XN-induced glioma cell death. With a microarray analysis, miR-204-3p was identified as the most upregulated miRNA induced by XN cytotoxicity. The extracellular signal-regulated kinase (ERK)/c-Fos pathway was validated to participate in XN-upregulated miR-204-3p expression. With a promoter assay and ChIP analysis, we found that c-Fos dose-dependently bound to the miR-204-3p gene promoter region. Furthermore, miR-204-3p levels decreased in several glioma cell lines compared to astrocytes. Overexpression of miR-204-3p enhanced glioma cell apoptosis. IGFBP2, an upregulated regulator of glioma proliferation, was validated by a TCGA analysis as a direct target gene of miR-204-3p. XN's inhibition of the IGFBP2/AKT/Bcl2 pathway via miR-204-3p targeting played a critical role in mediating glioma cell death. These results emphasized that the XN-mediated miR-204-3p network may provide novel therapeutic strategies for future glioblastoma therapy and drug development.

AB - Xanthohumol (XN), a prenylated chalcone extracted from hop plant Humulus lupulus L. (Cannabaceae), has potential for cancer therapy, including gliomas. Micro (mi)RNAs are small noncoding RNAs that control gene expression. Several miRNAs have been identified to participate in regulating glioma development. However, no studies have demonstrated whether miRNA is involved in XN cytotoxicity resulting in glioma cell death. This study investigated the effects of XN-mediated miRNA expression in activating apoptotic pathways in glioblastoma U87 MG cells. First, we found that XN significantly reduced cell viability and induced apoptosis via pro-caspase-3/8 cleavage and poly(ADP ribose) polymerase (PARP) degradation. We also identified that pro-caspase-9 cleavage, Bcl2 family expression changes, mitochondrial dysfunction, and intracellular ROS generation also participated in XN-induced glioma cell death. With a microarray analysis, miR-204-3p was identified as the most upregulated miRNA induced by XN cytotoxicity. The extracellular signal-regulated kinase (ERK)/c-Fos pathway was validated to participate in XN-upregulated miR-204-3p expression. With a promoter assay and ChIP analysis, we found that c-Fos dose-dependently bound to the miR-204-3p gene promoter region. Furthermore, miR-204-3p levels decreased in several glioma cell lines compared to astrocytes. Overexpression of miR-204-3p enhanced glioma cell apoptosis. IGFBP2, an upregulated regulator of glioma proliferation, was validated by a TCGA analysis as a direct target gene of miR-204-3p. XN's inhibition of the IGFBP2/AKT/Bcl2 pathway via miR-204-3p targeting played a critical role in mediating glioma cell death. These results emphasized that the XN-mediated miR-204-3p network may provide novel therapeutic strategies for future glioblastoma therapy and drug development.

KW - ERK/c-Fos pathway

KW - Glioblastoma

KW - IGFBP2

KW - miR-204-3p

KW - Xanthohumol

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