Oncol Res. 2017 Sep 21;25(8):1269-1282. doi: 10.3727/096504017X14850151453092. Epub 2017 Jan 23.
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.
微小 RNA（miRs）是一类小的非编码 RNA，通过诱导其靶基因的翻译抑制或降解来作为关键的基因调控因子。然而，miR-133b 调控肝细胞癌（HCC）生长和转移的机制在很大程度上仍不清楚。在这里，我们发现 miR-133b 在 HCC 组织和细胞系中显著下调。此外，miR-133b 水平低与 HCC 的恶性进展显著相关。LASP1 在 HCC 组织和细胞系中上调，然后被确定为 HCC HepG2 和 Hep3B 细胞中 miR-133b 的一个新靶标。此外，LASP1 的增加表达与 HCC 的进展有关。体外研究表明，miR-133b 的过表达抑制了 HepG2 和 Hep3B 细胞的增殖、迁移和侵袭。同样，LASP1 的敲低减少了 HepG2 和 Hep3B 细胞的增殖、迁移和侵袭。此外，LASP1 的过表达减弱了 miR-133b 对 HepG2 和 Hep3B 细胞恶性表型的抑制作用，表明 miR-133b 可能通过靶向 LASP1 抑制 HCC 的生长和转移。此外，miR-133b 的过表达抑制了 HepG2 和 Hep3B 细胞在体内的肿瘤生长。因此，miR-133b/LASP1 轴可能成为治疗 HCC 的一个潜在靶点。
