https://scholars.lib.ntu.edu.tw/handle/123456789/560390
標題: | Nuclear IKKα mediates microRNA-7/-103/107/21 inductions to downregulate maspin expression in response to HBx overexpression | 作者: | Chen W.-S. Liu L.-C. Yen C.-J. Chen Y.-J. Chen J.-Y. Ho C.-Y. Liu S.-H. CHING-CHOW CHEN Huang W.-C. |
關鍵字: | HBx; Hepatocellular carcinoma; IKKα; Maspin; MicroRNA | 公開日期: | 2016 | 卷: | 7 | 期: | 35 | 起(迄)頁: | 56309-56323 | 來源出版物: | Oncotarget | 摘要: | Maspin is a tumor suppressor that stimulates apoptosis and inhibits metastasis in various cancer types, including hepatocellular carcinoma (HCC). Our previous study has demonstrated that HBx induced microRNA-7, 103, 107, and 21 expressions to suppress maspin expression, leading to metastasis, chemoresistance, and poor prognosis in HCC patients. However, it remains unclear how HBx elicits these microRNA expressions. HBx has been known to induce aberrant activation and nuclear translocation of inhibitor-κB kinase-α (IKKα) to promote HCC progression. In this study, our data further revealed that nuclear IKKα expression was inversely correlated with maspin expression in HBVassociated patients. Nuclear IKKα but not IKKβ reduced maspin protein and mRNA expression, and inhibition of IKKα reverses HBx-mediated maspin downregulation and chemoresistance. In response to HBx overexpression, nuclear IKKα was further demonstrated to induce the gene expressions of microRNA-7, -103, -107, and -21 by directly targeting their promoters, thereby leading to maspin downregulation. These findings indicated nuclear IKKα as a critical regulator for HBx-mediated microRNA induction and maspin suppression, and suggest IKKα as a promising target to improve the therapeutic outcome of HCC patients. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/560390 | ISSN: | 19492553 | DOI: | 10.18632/oncotarget.10462 | SDG/關鍵字: | hepatitis B virus X protein; histone H3; I kappa B kinase alpha; I kappa B kinase beta; immunoglobulin enhancer binding protein; maspin; messenger RNA; microRNA; microRNA 103; microRNA 107; microRNA 21; microRNA 7; short hairpin RNA; unclassified drug; CHUK protein, human; hepatitis B virus X protein; histone; I kappa B kinase; IKBKB protein, human; messenger RNA; microRNA; serine proteinase inhibitor; SERPIN-B5; transactivator protein; tumor marker; 3' untranslated region; Article; cancer patient; cancer prognosis; cancer staging; cancer survival; cell viability; cellular distribution; chromatin immunoprecipitation; controlled study; down regulation; drug resistance; epigenetics; gene expression regulation; genetic transfection; hepatitis B; hepatocellular carcinoma cell line; human; human tissue; molecular dynamics; MTT assay; promoter region; protein DNA binding; protein expression; protein phosphorylation; RNA stability; RNA translation; transcription initiation; transcription initiation site; transcription regulation; upregulation; apoptosis; carcinogenesis; cell nucleus; disease exacerbation; genetics; HEK293 cell line; Hepatitis B virus; liver cell carcinoma; liver tumor; metabolism; pathology; phosphorylation; physiology; signal transduction; tumor cell line; tumor suppressor gene; virology; Apoptosis; Biomarkers, Tumor; Carcinogenesis; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Nucleus; Disease Progression; Down-Regulation; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Genes, Tumor Suppressor; HEK293 Cells; Hepatitis B virus; Histones; Humans; I-kappa B Kinase; Liver Neoplasms; MicroRNAs; Phosphorylation; RNA, Messenger; Serpins; Signal Transduction; Trans-Activators |
顯示於: | 藥理學科所 |
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