https://scholars.lib.ntu.edu.tw/handle/123456789/565147
標題: | Dysregulation of liver developmental microRNA contribute to hepatic carcinogenesis | 作者: | JIA-FENG WU MING-CHIH HO YEN-HSUAN NI HONG-YUAN HSU PO-HUANG LEE MEI-HWEI CHANG |
公開日期: | 2020 | 出版社: | Elsevier B.V. | 卷: | 119 | 期: | 6 | 起(迄)頁: | 1041-1051 | 來源出版物: | Journal of the Formosan Medical Association | 摘要: | Background/purpose: To investigate the role of microRNA (miRNA) dysregulation in liver cancer by assessing the miRNA profiles of human hepatic stem cells (HpSCs), marker-carrying human hepatoblastoma (HB) cells, and hepatocellular carcinoma (HCC) cells vs. those of fetal hepatocytes. Methods: We subjected human HCC and HB tumor specimens to immunohistochemical (IHC) staining for markers of HpSCs. We analyzed the miRNA patterns of HpSCs, HCC cells, HB cells, and fetal hepatocytes using microarray analysis, with confirmation via quantitative real-time polymerase chain reaction. The roles of the miRNAs in liver cancer stem cells (CSCs) were also elucidated. Results: The epithelial cell adhesion molecule (EpCAM) was the most prevalent HpSCs marker in human HB and HCC tumor cells and hepatoma cells. EpCAM-positive HB and HCC cells exhibited greater self-renewal and tumorigenicity than their EpCAM-negative counterparts or EpCAM-positive fetal hepatocytes. In EpCAM-positive fetal hepatocytes, miR-126 expression level increased with gestational age. The EpCAM-positive HB cells exhibited downregulation of miR-126 in comparison to EpCAM-positive fetal hepatocytes. An miR-126 mimic reduced sphere and colony formation in, and induced apoptosis of, HB cells. In comparison to EpCAM-positive fetal hepatocytes, EpCAM-positive HCC cells exhibited downregulation of miR-126, miR-144, and miR-451. Transfection of miR-126, miR-144, and miR-451 induced apoptosis of, and reduced sphere and colony formation in, HCC cells. Conclusion: Dysregulation of liver developmental miRNAs, which exert a tumor suppressant effect, in EpCAM-positive HpSCs may contribute to liver carcinogenesis by promoting the transformation of HpSCs to CSCs of HB and HCC. ? 2019 Formosan Medical Association |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85073514583&doi=10.1016%2fj.jfma.2019.09.018&partnerID=40&md5=67b7c4b1f83e36dca7300c2c7399eba1 https://scholars.lib.ntu.edu.tw/handle/123456789/565147 |
ISSN: | 0929-6646 | DOI: | 10.1016/j.jfma.2019.09.018 | SDG/關鍵字: | epithelial cell adhesion molecule; microRNA; microRNA 126; microRNA 144; microRNA 451; unclassified drug; microRNA; animal experiment; animal model; animal tissue; apoptosis; Article; cancer stem cell; carcinogenicity; cell self-renewal; colony formation; controlled study; down regulation; female; fetus; gene expression level; genetic regulation; gestational age; Hep 3B2.1-7 cell line; Hep-G2 cell line; HuH-6 cell line; Huh-7 cell line; human; human cell; human tissue; immunohistochemistry; liver cancer; liver carcinogenesis; Mahlavu cell line; male; microarray analysis; mouse; nonhuman; real time polymerase chain reaction; tumor spheroid; carcinogenesis; genetics; liver cell carcinoma; liver tumor; metabolism; tumor cell line; Carcinogenesis; Carcinoma, Hepatocellular; Cell Line, Tumor; Humans; Liver Neoplasms; MicroRNAs |
顯示於: | 醫學教育暨生醫倫理學科所 |
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