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microRNA-193b 调控人肝癌细胞的增殖、迁移和侵袭。

MicroRNA-193b regulates proliferation, migration and invasion in human hepatocellular carcinoma cells.

机构信息

Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, People's Republic of China.

出版信息

Eur J Cancer. 2010 Oct;46(15):2828-36. doi: 10.1016/j.ejca.2010.06.127. Epub 2010 Jul 23.

Abstract

BACKGROUND AND AIMS

Recently, some miRNAs have been reported to be connected closely with the development of human hepatocellular carcinoma. However, the functions of these miRNAs in HCC remain largely undefined.

METHODS

The expression profiles of miR-193b were compared between HCC tissues and adjacent normal liver tissues using qRT-PCR method. This method was also be used to screen the potential target genes of miR-193b. A luciferase reporter assay was conducted to confirm target association. Finally, the functional effect of miR-193b in hepatoma cells was examined further.

RESULTS

miR-193b was significantly down-regulated in most of the HCC tissues compared to the matching non-tumoural liver tissues. Furthermore, ectopic expression of miR-193b dramatically suppressed the ability of hepatoma cells to form colonies in vitro and to develop tumours in nude mice. CCND1 and ETS1 were revealed to be regulated by miR-193b directly. By regulating the expressions of these oncogenes, miR-193b induced cell cycle arrest and inhibited the invasion and migration of hepatoma cells.

CONCLUSIONS

miR-193b may function as a tumour suppressor in the development of HCC by acting on multiple tumourigenic pathways.

摘要

背景与目的

最近,一些 miRNA 与人类肝细胞癌的发生发展密切相关。然而,这些 miRNA 在 HCC 中的作用在很大程度上仍未确定。

方法

采用 qRT-PCR 方法比较 HCC 组织和相邻正常肝组织中 miR-193b 的表达谱。该方法还用于筛选 miR-193b 的潜在靶基因。通过荧光素酶报告基因检测证实了靶基因的相关性。最后,进一步检测了 miR-193b 在肝癌细胞中的功能效应。

结果

与匹配的非肿瘤性肝组织相比,miR-193b 在大多数 HCC 组织中表达显著下调。此外,外源性表达 miR-193b 可显著抑制肝癌细胞在体外形成集落和在裸鼠中形成肿瘤的能力。CCND1 和 ETS1 被证实可被 miR-193b 直接调控。通过调节这些癌基因的表达,miR-193b 诱导细胞周期停滞,并抑制肝癌细胞的侵袭和迁移。

结论

miR-193b 可能通过作用于多种致瘤途径,在 HCC 的发生发展中发挥肿瘤抑制作用。

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