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微小 RNA-9 降低 SK-Hep-1 细胞的侵袭能力和 E-钙黏蛋白分泌。

MicroRNA-9 reduces cell invasion and E-cadherin secretion in SK-Hep-1 cell.

机构信息

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510080, China.

出版信息

Med Oncol. 2010 Sep;27(3):654-60. doi: 10.1007/s12032-009-9264-2. Epub 2009 Jul 2.

Abstract

MicroRNAs (miRNAs) are an abundant class of short noncoding RNAs that can posttranscriptionally regulate gene expression in animals. They are also involved in cancer initiation and progression, and their expression profiles serve as phenotypic signatures of different cancers. The roles played by microRNAs specifically in "micromanagement of metastasis" has been addressed only recently. The molecular mechanisms of hepatocellular carcinoma (HCC) metastasis are still poorly understood. Recent evidence implies genetic determinants of cancer metastasis. Because gene expression signature significantly differs between primary metastasis-free HCC and primary HCC with intrahepatic metastases, miRNA expression in those primary HCC may change correspondingly. The 28 up-regulated miRNAs, part of the reported miRNA profiles of HCC, were compared in primary HCC with or without metastases. Only eight miRNAs were found to be significantly up-regulated in primary HCC with metastases while miR-9 had the highest hold change. miR-9 was highly expressed in SK-Hep-1 cell when compared with other hepatoma cell lines and downregulation of miR-9 reduced SK-Hep-1 cell invasion. E-cadherin, a tumor invasion suppressor in HCC, was found to be a putative gene target of miR-9. E-cadherin was up-regulated by miR-9 inhibitor. The findings suggest miR-9 could be involved in HCC metastasis.

摘要

微小 RNA(miRNAs)是一类丰富的短非编码 RNA,可在后转录水平调节动物基因的表达。它们也参与癌症的起始和进展,其表达谱可作为不同癌症的表型特征。miRNAs 在“转移的微观管理”中所扮演的角色最近才被提出。肝细胞癌(HCC)转移的分子机制仍知之甚少。最近的证据表明癌症转移存在遗传决定因素。由于原发性无转移 HCC 和原发性 HCC 伴肝内转移之间的基因表达谱显著不同,这些原发性 HCC 中的 miRNA 表达可能相应改变。在原发性 HCC 中比较了有或没有转移的 28 个上调 miRNA,这些 miRNA 是 HCC 报道 miRNA 谱的一部分。结果发现,只有 8 个 miRNA 在伴转移的原发性 HCC 中显著上调,而 miR-9 的变化倍数最高。与其他肝癌细胞系相比,miR-9 在 SK-Hep-1 细胞中高表达,下调 miR-9 可降低 SK-Hep-1 细胞的侵袭能力。E-钙黏蛋白是 HCC 中的肿瘤侵袭抑制因子,被发现是 miR-9 的一个潜在基因靶标。miR-9 抑制剂可上调 E-钙黏蛋白。研究结果提示 miR-9 可能参与 HCC 转移。

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