MicroRNA-1 Suppresses Tumor Progression and UHRF1 Expression in Cholangiocarcinoma.

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作者:Muto Makoto, Ishigame Teruhide, Kimura Takashi, Sato Naoya, Kofunato Yasuhide, Kenjo Akira, Yamamoto Hiroyuki, Yokoyama Yuhki, Yamamoto Hirofumi, Marubashi Shigeru
MicroRNAs (miRNAs) have been shown to suppress tumor progression in several cancers, including cholangiocarcinoma; however, their mechanisms and roles remain largely unexplored. In this study, we aimed to identify novel miRNAs and molecules associated with cholangiocarcinoma progression. Using miRNA and mRNA microarrays from surgically resected specimens, we identified microRNA-1 (miR-1) as significantly downregulated in cholangiocarcinoma tissues and selected it for further analysis. In the in vitro assay, miR-1 was transfected into cholangiocarcinoma cell lines to assess its effect on tumor progression. Proliferation and migration/invasion assays demonstrated significant tumor suppression in miR-1-transfected cells. Additionally, cell cycle and apoptosis assays revealed an increase in cells in the G1 and G2/M phases, a decrease in the S phase, and an elevation in apoptosis rates in miR-1-transfected cells. Further analysis of the miRNA and mRNA microarray data identified ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) as a molecule potentially associated with miR-1. Quantitative RT-PCR and Western blotting analysis confirmed that UHRF1 expression was suppressed following miR-1 transfection. This study demonstrated that cholangiocarcinoma progression was suppressed by restoring miR-1 expression, suggesting that UHRF1 expression is involved in cholangiocarcinoma progression. The results of this study provide new insights into the molecular mechanisms underlying cholangiocarcinoma progression.

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