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Interplay between ceRNA and Epigenetic Control of microRNA: Modelling Approaches with Application to the Role of Estrogen in Ovarian Cancer.
Huang, Tzy-Wei; Cheng, Frank H C; Yan, Ching-Cher Sanders; Chuang, Yu-Ming; Cho, Chien-Hong; Lai, Hung-Cheng; Shieh, Shih-Feng; Chan, Michael W Y; Tsai, Je-Chiang.
Afiliação
  • Huang TW; Department of Mathematics, National Chung Cheng University, Min-Hsiung, Chia-Yi 621, Taiwan.
  • Cheng FHC; Department of Biomedical Sciences, National Chung Cheng University, Min-Hsiung, Chia-Yi 621, Taiwan.
  • Yan CS; Epigenomics and Human Disease Research Center, National Chung Cheng University, Min-Hsiung, Chia-Yi 621, Taiwan.
  • Chuang YM; Indiana University School of Medicine-Bloomington, Indiana University, Bloomington, IN 47405, USA.
  • Cho CH; Institute of Chemistry, Academia Sinica, Nangang District, Taipei 115, Taiwan.
  • Lai HC; Department of Biomedical Sciences, National Chung Cheng University, Min-Hsiung, Chia-Yi 621, Taiwan.
  • Shieh SF; Epigenomics and Human Disease Research Center, National Chung Cheng University, Min-Hsiung, Chia-Yi 621, Taiwan.
  • Chan MWY; Department of Applied Mathematics, National Sun Yat-Sen University, Gushan District, Kaohsiung 804, Taiwan.
  • Tsai JC; Department of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, Zhonghe District, Taipei 235, Taiwan.
Int J Mol Sci ; 23(4)2022 Feb 18.
Article em En | MEDLINE | ID: mdl-35216394
MicroRNAs (miRNAs) play an important role in gene regulation by degradation or translational inhibition of the targeted mRNAs. It has been experimentally shown that the way miRNAs interact with their targets can be used to explain the indirect interactions among their targets, i.e., competing endogenous RNA (ceRNA). However, whether the protein translated from the targeted mRNAs can play any role in this ceRNA network has not been explored. Here we propose a deterministic model to demonstrate that in a network of one miRNA interacting with multiple-targeted mRNAs, the competition between miRNA-targeted mRNAs is not sufficient for the significant change of those targeted mRNA levels, while dramatic changes of these miRNA-targeted mRNAs require transcriptional inhibition of miRNA by its target proteins. When applied to estrogen receptor signaling pathways, the miR-193a targets E2F6 (a target of estrogen receptor), c-KIT (a marker for cancer stemness), and PBX1 (a transcriptional activator for immunosuppressive cytokine, IL-10) in ovarian cancer, such that epigenetic silencing of miR-193a by E2F6 protein is required for the significant change of c-KIT and PBX1 mRNA level for cancer stemness and immunoevasion, respectively, in ovarian cancer carcinogenesis.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / RNA Mensageiro / MicroRNAs / Epigênese Genética / Estrogênios / Redes Reguladoras de Genes / RNA Longo não Codificante Limite: Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / RNA Mensageiro / MicroRNAs / Epigênese Genética / Estrogênios / Redes Reguladoras de Genes / RNA Longo não Codificante Limite: Female / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article