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首页> 外文期刊>Cell death & disease. >circHIPK3 regulates cell proliferation and migration by sponging miR-124 and regulating AQP3 expression in hepatocellular carcinoma
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circHIPK3 regulates cell proliferation and migration by sponging miR-124 and regulating AQP3 expression in hepatocellular carcinoma

机译:circHIPK3通过使miR-124变海绵并调节AQP3在肝细胞癌中的表达来调节细胞增殖和迁移

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摘要

Noncoding RNAs plays an important role in hepatocellular carcinoma (HCC). Here, we show that miR-124 was downregulated in HCC tissues and that the ectopic expression of miR-124 inhibited the proliferation and migration of HCC cells. We proposed that aquaporin 3 (AQP3) is a direct target of miR-124. AQP3 was upregulated in HCC tissues and inversely correlated with miR-124 expression. The overexpression of miR-124 decreased AQP3 expression. Indeed, AQP3 overexpression promoted cell proliferation and migration, whereas miR-124 knockdown suppressed cell proliferation and migration. Furthermore, we found that circular RNA HIPK3 (circHIPK3) acted as a miR-124 sponge and regulated the expression of the miR-124 target gene AQP3. circHIPK3 was upregulated in HCC tissues and positively correlated with AQP3 expression. Thus, silencing circHIPK3 inhibited cell proliferation and migration by downregulating AQP3 expression. Moreover, miR-124 inhibition rescued circHIPK3 knockdown induced reduction in cell proliferation and migration, as well as AQP3 expression. In vivo experiments also confirmed that circHIPK3 regulated xenograft tumor growth via the miR-124-AQP3 axis. These observations indicate a possible novel therapeutic strategy involving circular RNAs in HCC.
机译:非编码RNA在肝细胞癌(HCC)中起重要作用。在这里,我们显示miR-124在HCC组织中被下调,而miR-124的异位表达抑制了HCC细胞的增殖和迁移。我们提出水通道蛋白3(AQP3)是miR-124的直接目标。 AQP3在肝癌组织中上调,与miR-124表达呈负相关。 miR-124的过表达降低了AQP3表达。确实,AQP3过表达促进细胞增殖和迁移,而miR-124抑制基因抑制细胞增殖和迁移。此外,我们发现环状RNA HIPK3(circHIPK3)充当miR-124海绵并调节miR-124目标基因AQP3的表达。 circHIPK3在肝癌组织中上调,并与AQP3表达正相关。因此,沉默circHIPK3通过下调AQP3表达来抑制细胞增殖和迁移。此外,miR-124抑制可挽救circHIPK3敲低诱导的细胞增殖和迁移以及AQP3表达的减少。体内实验还证实,circHIPK3通过miR-124-AQP3轴调节异种移植肿瘤的生长。这些观察结果表明一种可能的新型治疗策略涉及HCC中的环状RNA。

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