https://scholars.lib.ntu.edu.tw/handle/123456789/513753
標題: | miRNA-7/21/107 contribute to HBx-induced hepatocellular carcinoma progression through suppression of maspin | 作者: | Chen W.-S. Yen C.-J. Chen Y.-J. Chen J.-Y. Wang L.-Y. Chiu S.-J. Shih W.-L. Ho C.-Y. TZU-TANG WEI Pan H.-L. Chien P.-H. Hung M.-C. CHING-CHOW CHEN Huang W.-C. |
公開日期: | 2015 | 卷: | 6 | 期: | 28 | 起(迄)頁: | 25962-25974 | 來源出版物: | Oncotarget | 摘要: | Maspin suppresses tumor progression by promoting cell adhesion and apoptosis and by inhibiting cell motility. However, its role in tumorigenesis of hepatocellular carcinoma (HCC) remains unclear. The gene regulation of maspin and its relationship with HCC patient prognosis were investigated in this study. Maspin expression was specifically reduced in HBV-associated patients and correlated with their poor prognosis. Maspin downregulation in HCC cells was induced by HBx to promote their motility and resistance to anoikis and chemotherapy. HBx-dependent induction of microRNA-7, -107, and -21 was further demonstrated to directly target maspin mRNA, leading to its protein downregulation. Higher expressions of these microRNAs also correlated with maspin downregulation in HBV-associated patients, and were associated with their poor overall survival. These data not only provided new insights into the molecular mechanisms of maspin deficiency by HBx, but also indicated that downregulation of maspin by microRNAs confers HBx-mediated aggressiveness and chemoresistance in HCC. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/513753 | ISSN: | 19492553 | DOI: | 10.18632/oncotarget.4504 | SDG/關鍵字: | maspin; messenger RNA; microRNA; microRNA 103; microRNA 107; microRNA 21; microRNA 7; unclassified drug; 3' untranslated region; antineoplastic agent; hepatitis B virus X protein; microRNA; MIRN107 microRNA, human; MIRN21 microRNA, human; MIRN7 microRNA, human; serine proteinase inhibitor; SERPIN-B5; transactivator protein; anoikis; Article; cancer growth; cancer prognosis; cancer survival; controlled study; disease free survival; down regulation; drug resistance; embryo; gene; gene expression; human; human cell; human tissue; liver cell carcinoma; major clinical study; maspin gene; overall survival; protein expression; 3' untranslated region; cell survival; disease course; drug effects; female; gene expression profiling; gene expression regulation; genetics; HEK293 cell line; Hep-G2 cell line; Hepatitis B virus; host pathogen interaction; liver cell carcinoma; liver tumor; male; metabolism; multivariate analysis; physiology; procedures; reverse transcription polymerase chain reaction; tumor cell line; virology; Western blotting; 3' Untranslated Regions; Anoikis; Antineoplastic Agents; Blotting, Western; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; Disease Progression; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; HEK293 Cells; Hep G2 Cells; Hepatitis B virus; Host-Pathogen Interactions; Humans; Liver Neoplasms; Male; MicroRNAs; Multivariate Analysis; Reverse Transcriptase Polymerase Chain Reaction; Serpins; Trans-Activators |
顯示於: | 藥理學科所 |
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