Global assessment of Antrodia cinnamomea-induced microRNA alterations in hepatocarcinoma cells

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Title:	Global assessment of Antrodia cinnamomea-induced microRNA alterations in hepatocarcinoma cells
Authors:	馬念涵;Chen, Yen-Ju;Thang, Mike W. C.;Chan, Yu-Tzu;Huang, Yu-Feng;Ma, Nianhan;Yu, Alice L.;Wu, Chung-Yi;Hu, Miao-Lin;Chiu, Kuo Ping
Contributors:	生醫理工學院生醫科學與工程學系
Keywords:	1-Phosphatidylinositol 3-kinase;AKT protein;Analysis;Anticancer properties;Antrodia - chemistry;Apoptosis;Biodegradation;c-Jun protein;Cancer;Carcinoma, Hepatocellular - genetics;Carcinoma, Hepatocellular - pathology;Cell death;Cell survival;Complex Mixtures - pharmacology;Degradation;Fruit bodies;Fruiting Bodies, Fungal - chemistry;Gene expression;Gene Expression Profiling;Gene Expression Regulation, Neoplastic - drug effects;Gene sequencing;Genomes;Genomics;Hepatocytes;Humans;Kinases;Liver;Liver cancer;Liver Neoplasms - genetics;Liver Neoplasms - pathology;MAP kinase;MicroRNA;MicroRNAs - genetics;miRNA;Pathways;Phosphorylation;Proteins;Ribonucleic acid;RNA;Signaling;Transcription factors;Transcriptome - drug effects;Tumor Cells, Cultured;Western blotting
Date:	2013-12-17
Issue Date:	2026-04-23 11:16:11 (UTC+8)
Publisher:	Public Library of Science;United States: Public Library of Science
Abstract:	摘要： Recent studies have demonstrated a potent anticancer potential of medicinal fungus Antrodia cinnamomea, especially against hepatocarcinoma. These studies, however, were performed with prolonged treatments, and the early anticancer events remain missing. To probe the early anticancer mechanisms of A. cinnamomea, we treated SK-Hep-1 liver cancer cell with A. cinnamomea fruiting body extract for 2 and 4 hours, sequenced RNA samples with next-generation sequencing approach, and profiled the genome-wide miRNA and mRNA transcriptomes. Results unmistakably associated the early anticancer effect of A. cinnamomea fruiting body extract with a global downregulation of miRNAs which occurred solely in the A. cinnamomea fruiting body extract-treated SK-Hep-1 cells. Moreover, the inhibitory effect of A. cinnamomea fruiting body extract upon cancer miRNAs imposed no discrimination against any particular miRNA species, with oncomirs miR-21, miR-191 and major oncogenic clusters miR-17-92 and miR-106b-25 among the most severely downregulated. Western blotting further indicated a decrease in Drosha and Dicer proteins which play a key role in miRNA biogenesis, together with an increase of XRN2 known to participate in miRNA degradation pathway. Transcriptome profiling followed by GO and pathway analyses indicated that A. cinnamomea induced apoptosis, which was tightly associated with a downregulation of PI3K/AKT and MAPK pathways. Phosphorylation assay further suggested that JNK and c-Jun were closely involved in the apoptotic process. Taken together, our data indicated that the anticancer effect of A. cinnamomea can take place within a few hours by targeting multiple proteins and the miRNA system. A. cinnamomea indiscriminately induced a global downregulation of miRNAs by simultaneously inhibiting the key enzymes involved in miRNA maturation and activating XRN2 protein involved in miRNA degradation. Collapsing of the miRNA system together with downregulation of cell growth and survival pathways and activation of JNK signaling unleash the extrinsic and intrinsic apoptosis pathways, leading to the cancer cell death. 其他題名： PLoS One 出版者： United States: Public Library of Science 出版日期： 2013-12-17 出處： PloS one, 2013-12, Vol.8 (12), p.e82751 資源來源： Agricultural & Environmental Science Collection 版權： COPYRIGHT 2013 Public Library of Science 版權： 2013 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 版權： 2013 Chen et al 2013 Chen et al 識別號： ISSN: 1932-6203 識別號： EISSN: 1932-6203 識別號： DOI: 10.1371/journal.pone.0082751 識別號： PMID: 24358224
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