MicroRNA-133b Inhibits Proliferation, Cellular Migration, and Invasion via Targeting LASP1 in Hepatocarcinoma Cells.

MicroRNA-133b Inhibits Proliferation, Cellular Migration, and Invasion via Targeting LASP1 in Hepatocarcinoma Cells.
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DOI:
10.3727/096504017x14850151453092
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发表时间:
2017-09-21
期刊:
影响因子:
3.1
通讯作者:
Tang J
Tang J
中科院分区:
医学2区
文献类型:
--
作者:
Li H;Xiang Z;Liu Y;Xu B;Tang J

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microRNAs(miRs)是一类小分子非编码RNA,通过诱导靶基因的翻译抑制或降解而发挥重要的基因调控作用。然而,miR-133 b在肝细胞癌(HCC)生长和转移中的调控机制仍不清楚。我们发现miR-133 b在HCC组织和细胞系中显著下调。此外,低miR-133 b水平与HCC的恶性进展显著相关。LASP 1在HCC组织和细胞系中上调,然后被鉴定为HCC HepG 2和Hep 3B细胞中miR-133 b的新靶点。此外,LASP 1的表达增加与HCC进展相关。体外研究表明,miR-133 b过表达抑制HepG 2和Hep 3B细胞的增殖、迁移和侵袭。类似地,LASP 1的敲低降低了HepG 2和Hep 3B细胞的增殖、迁移和侵袭。此外,过表达LASP 1减弱了miR-133 b对HepG 2和Hep 3B细胞恶性表型的抑制作用,表明miR-133 b可能通过靶向LASP 1抑制HCC的生长和转移。此外,miR-133 b的过表达抑制体内HepG 2和Hep 3B细胞的肿瘤生长。因此,miR-133 b/LASP 1轴可能成为HCC治疗的潜在靶点。
MicroRNAs (miRs), a class of small noncoding RNAs, are key gene regulators through inducing translational repression or degradation of their target genes. However, the regulatory mechanism of miR-133b underlying hepatocellular carcinoma (HCC) growth and metastasis remains largely unclear. Here we found that miR-133b was significantly downregulated in HCC tissues and cell lines. Moreover, low miR-133b levels were significantly associated with the malignant progression of HCC. LASP1, upregulated in HCC tissues and cell lines, was then identified as a novel target of miR-133b in HCC HepG2 and Hep3B cells. Moreover, the increased expression of LASP1 was associated with HCC progression. An in vitro study showed that overexpression of miR-133b inhibited the proliferation, migration, and invasion of HepG2 and Hep3B cells. Similarly, knockdown of LASP1 reduced HepG2 and Hep3B cell proliferation, migration, and invasion. Furthermore, overexpression of LASP1 attenuated the suppressive effect of miR-133b on the malignant phenotypes of HepG2 and Hep3B cells, suggesting that miR-133b may inhibit HCC growth and metastasis via targeting LASP1. In addition, overexpression of miR-133b inhibits tumor growth of HepG2 and Hep3B cells in vivo. Therefore, the miR-133b/LASP1 axis may become a potential target for the treatment of HCC.