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微小 RNA-590-5p 通过靶向 TGF-β RII 调节人肝癌细胞的增殖和侵袭。

MicroRNA-590-5p regulates proliferation and invasion in human hepatocellular carcinoma cells by targeting TGF-β RII.

机构信息

Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital of Guangzhou Medical College, Guangzhou, China.

出版信息

Mol Cells. 2012 Jun;33(6):545-51. doi: 10.1007/s10059-012-2267-4. Epub 2012 Jun 7.

Abstract

MicroRNAs (miRNAs) are regulatory small non-coding RNAs that can regulate gene expression by binding to gene elements, such as the gene promotor 5'UTR, mainly in the 3'UTR of mRNA. One miRNA targets many mRNAs, which can be regulated by many miRNAs, leading to a complex metabolic network. In our study, we found that the expression level of miR-590-5p is higher in the human hepatocellular carcinoma cell line HepG2 than in the normal hepatocellular cell line L02. Downregulation of miR-590-5p inhibited proliferation and invasion of hepatocellular carcinoma cells (HCCs). We also showed that expression of TGF-beta RII, which has been regarded as a regulator of tumor proliferation, invasion, and migration in hepatocellular carcinoma, is regulated by miRNA-590-5p. In addition, miR-590-5p downregulated the expression of TGF-beta RII by targeting the 3'UTR of mRNA. We also found that downregulation of miR-590-5p was associated with an elevation of TGF-beta RII and inhibition of proliferation and invasion in HepG2 cells. Furthermore, overexpression of miR-590-5p was associated with upregulation of TGF-beta RII and could promote proliferation and invasion in L02 cells. In conclusion, we determined that TGF-beta RII is a novel target of miRNA-590-5p. Thus, the role of TGF-beta RII in regulating proliferation and invasion of human HCCs is controlled by miR-590-5p. In other words, miR-590-5p promotes proliferation and invasion in human HCCs by directly targeting TGF-beta RII.

摘要

微小 RNA(miRNA)是调节基因表达的小非编码 RNA,可以通过与基因元件结合来调节基因表达,如基因启动子 5'UTR,主要在 mRNA 的 3'UTR 中。一个 miRNA 可以靶向许多 mRNAs,而许多 miRNA 可以调节这些 mRNAs,从而导致复杂的代谢网络。在我们的研究中,我们发现 miR-590-5p 在人肝癌细胞系 HepG2 中的表达水平高于正常肝细胞系 L02。下调 miR-590-5p 抑制肝癌细胞(HCCs)的增殖和侵袭。我们还表明,TGF-β RII 的表达被 miR-590-5p 调节,TGF-β RII 被认为是肝癌中肿瘤增殖、侵袭和迁移的调节剂。此外,miR-590-5p 通过靶向 mRNA 的 3'UTR 下调 TGF-β RII 的表达。我们还发现下调 miR-590-5p 与 TGF-β RII 的升高以及 HepG2 细胞增殖和侵袭的抑制有关。此外,miR-590-5p 的过表达与 TGF-β RII 的上调有关,并可促进 L02 细胞的增殖和侵袭。总之,我们确定 TGF-β RII 是 miRNA-590-5p 的一个新靶标。因此,miR-590-5p 调节人 HCCs 增殖和侵袭的作用受 TGF-β RII 控制。换句话说,miR-590-5p 通过直接靶向 TGF-β RII 促进人 HCCs 的增殖和侵袭。

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