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首页> 外文期刊>Journal of cellular biochemistry. >MicroRNA 21-mediated suppression of sprouty1 by Pokemon affects liver cancer cell growth and proliferation
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MicroRNA 21-mediated suppression of sprouty1 by Pokemon affects liver cancer cell growth and proliferation

机译：宠物小精灵的MicroRNA 21介导的抑制budyy1影响肝癌细胞的生长和增殖

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Transcriptional repressor Pokemon is a critical factor in embryogenesis, development, cell proliferation, differentiation, and oncogenesis, thus behaving as an oncogene. Oncomine database suggests a potential correlation between the expressions of Pokemon and Sprouty1. This study investigated the regulatory role of Pokemon in Sprouty1 expression and the effect on liver cancer cell growth and proliferation, revealing a novel miR-21-mediated regulatory circuit. In normal (HL-7702) and cancer (QGY-7703) liver cell lines, Sprouty1 expression is inversely correlated with Pokemon levels. Targeted expression or siRNA-mediated silencing showed that Pokemon is a repressor of Sprouty1 expression at both mRNA and protein levels, but Pokemon cannot affect the promoter activity of Sprouty1. Sprouty1 is a target of miR-21 and interestingly, we found that miR-21 is up-regulated by Pokemon in liver cancer cells. Luciferase reporter assays showed that Pokemon up-regulated miR-21 transcription in a dose-dependent manner, and ChIP assay exhibited a direct binding of Pokemon to the miR-21 promoter at -747 to -399 bp. Site-directed mutagenesis of the GC boxes at -684 to -679 bp and -652 to -647 bp of miR-21 promoter abolished the regulatory activity by Pokemon. Furthermore, we found that the modulation of Pokemon and miR-21 expression affected the growth and proliferation of liver cancer cells QGY-7703. In summary, our findings demonstrate that Pokemon suppresses Sprouty1 expression through a miR-21-mediated mechanism, affecting the growth and proliferation of liver cancer cells. This study recognized miR-21 and Sprouty1 as novel targets of the Pokemon regulatory network.
机译：转录抑制因子口袋妖怪是胚胎发生，发展，细胞增殖，分化和癌发生的关键因素，因此表现为癌基因。 Oncomine数据库表明Pokemon和Sprouty1的表达之间存在潜在的相关性。这项研究调查了口袋妖怪在Sprouty1表达中的调控作用以及对肝癌细胞生长和增殖的影响，揭示了一种新型的miR-21介导的调控电路。在正常（HL-7702）和癌症（QGY-7703）肝细胞系中，Sprouty1表达与口袋妖怪水平成反比。靶向表达或siRNA介导的沉默表明，口袋妖怪在mRNA和蛋白质水平上都是Sprouty1表达的阻遏物，但Pokemon不能影响Sprouty1的启动子活性。 Sprouty1是miR-21的靶标，有趣的是，我们发现miR-21在肝脏癌细胞中被口袋妖怪上调。萤光素酶报告基因检测显示，口袋妖怪以剂量依赖的方式上调了miR-21的转录，而ChIP检测显示出口袋妖怪在-747至-399 bp处直接与miR-21启动子结合。在miR-21启动子的-684至-679 bp和-652至-647 bp处发生GC盒的定点诱变消除了Pokemon的调节活性。此外，我们发现口袋妖怪和miR-21表达的调节影响肝癌细胞QGY-7703的生长和增殖。总之，我们的发现表明，口袋妖怪通过miR-21介导的机制抑制Sprouty1表达，从而影响肝癌细胞的生长和增殖。这项研究认为miR-21和Sprouty1是口袋妖怪监管网络的新型目标。

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