https://scholars.lib.ntu.edu.tw/handle/123456789/543475
標題: | Elevated p53 promotes the processing of miR-18a to decrease estrogen receptor-α in female hepatocellular carcinoma | 作者: | Li C.-L. KUN-HUEI YEH Liu W.-H. CHI-LING CHEN DING-SHINN CHEN PEI-JER CHEN Shiou-Hwei Yeh |
公開日期: | 2015 | 出版社: | Wiley-Liss Inc. | 卷: | 136 | 期: | 4 | 起(迄)頁: | 761-770 | 來源出版物: | International Journal of Cancer | 摘要: | The estrogen pathway has long been implicated as a tumor protector in female hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Our previous study identified that estrogen receptor alpha (ERα) protein is downregulated in 60% of female HCC cases, via a miR-18a elevation mediated suppression of ERa translation. This study aims to delineate the mechanism underlying the upregulation of miR-18a in female HCC. The analysis of 77 female HCC specimens revealed that miR-18a levels were associated with pre-miR-18a rather than pri-miR-18a levels, suggesting an enhanced processing of pri- to pre-miR-18a. Among a panel of factors involved in microRNA processing, p53 was identified as a novel regulator for miR-18a maturation process. Knockdown of p53 by si-RNA decreased the level of miR-18a, whereas overexpression of either wild-type or mutant p53 increased its level. The association between the elevation of miR-18a and the accumulation of p53, mainly caused by somatic mutations, was confirmed in the clinical specimens of HBV-related female HCC. By analyzing the association with clinicopathological features, activation of this p53/miR-18a pathway mainly occurs in younger or noncirrhosis female HCC patients and associated with a trend of worse overall survival. Therefore, this study demonstrated a novel function of elevated/mutant p53 in regulating the amount of ERα protein through its promoting the biogenesis of miR-18a, which could lead to decrease the tumor-protective function of the estrogen pathway in female hepatocarcinogenesis. ? 2014 UICC. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84918838312&doi=10.1002%2fijc.29052&partnerID=40&md5=43becf87ec6ee164b4e50205cca3b40f https://scholars.lib.ntu.edu.tw/handle/123456789/543475 |
ISSN: | 0020-7136 | DOI: | 10.1002/ijc.29052 | SDG/關鍵字: | estrogen receptor alpha; microRNA; microRNA 18a; protein p53; small interfering RNA; unclassified drug; estrogen receptor alpha; estrogen receptor alpha, human; microRNA; MIRN18 microRNA, human; protein p53; TP53 protein, human; adult; Article; biogenesis; cancer survival; carcinogenic activity; controlled study; female; gene expression regulation; genetic association; Hepatitis B virus; human; human tissue; liver carcinogenesis; liver cell carcinoma; major clinical study; male; mutant; overall survival; protein expression; protein function; RNA processing; signal transduction; somatic mutation; upregulation; wild type; aged; genetics; liver cell carcinoma; liver tumor; metabolism; middle aged; mutation; RNA interference; sexual development; Adult; Aged; Carcinoma, Hepatocellular; Estrogen Receptor alpha; Female; Gene Expression Regulation, Neoplastic; Humans; Liver Neoplasms; Male; MicroRNAs; Middle Aged; Mutation; RNA Interference; RNA Processing, Post-Transcriptional; Sex Characteristics; Tumor Suppressor Protein p53 |
顯示於: | 腫瘤醫學研究所 |
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