Zhang Yingying, Yang Xucheng, Wu Haijun, Zhou Weibin, Liu Zhenzhen
Department of Oncology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Department of Orthopedics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China.
Mol Med Rep. 2015 Oct;12(4):6193-8. doi: 10.3892/mmr.2015.4163. Epub 2015 Jul 31.
MicroRNA (miR)-145 has been shown to act as a suppressor in numerous cancer types, including non-small-cell lung cancer (NSCLC). Fascin 1 (FSCN1), an actin bundling protein, has been implicated in NSCLC. However, the detailed role of miR-145 as well as the association between miR-145 and FSCN1 in the regulation of migration and invasion in NSCLC cells has remained elusive. The present study revealed that miR-145 was downregulated and FSCN1 was upregulated in NSCLC tissues and cell lines. Further investigation showed that overexpression of miR-145 markedly inhibited the protein expression of FSCN1, while knockdown of miR-145 upregulated the protein (but not mRNA) levels of FSCN1 in the NSCLC cell line H129. Moreover, a luciferase reporter assay indicated that FSCN1 is a direct target of miR-145 in NSCLC H129 cells. Furthermore, overexpression of miR-145 markedly inhibited the migration and invasion of NSCLC cells, similar to the effect of small interfering RNA-mediated FSCN1 inhibition in H129 cells. In addition, the inhibitory effect of miR-145 overexpression on migration and invasion was reversed by FSCN1 upregulation in H129 cells. These findings suggested that miR-145 has an inhibitory effect on the migration and invasion in NSCLC cells, at least in part through suppressing the protein expression of its target FSCN1. Therefore, miR-145/FSCN1 may be used as a potential target for the treatment of NSCLC.
微小RNA(miR)-145已被证明在包括非小细胞肺癌(NSCLC)在内的多种癌症类型中发挥抑制作用。肌动蛋白成束蛋白Fascin 1(FSCN1)与NSCLC有关。然而,miR-145的具体作用以及miR-145与FSCN1在NSCLC细胞迁移和侵袭调节中的关联仍不清楚。本研究表明,NSCLC组织和细胞系中miR-145表达下调,FSCN1表达上调。进一步研究表明,miR-145过表达显著抑制FSCN1的蛋白表达,而在NSCLC细胞系H129中敲低miR-145则上调FSCN1的蛋白(而非mRNA)水平。此外,荧光素酶报告基因检测表明,FSCN1是NSCLC H129细胞中miR-145的直接靶标。此外,miR-145过表达显著抑制NSCLC细胞的迁移和侵袭,类似于小干扰RNA介导的H129细胞中FSCN1抑制的效果。此外,H129细胞中FSCN1上调可逆转miR-145过表达对迁移和侵袭的抑制作用。这些发现表明,miR-145对NSCLC细胞的迁移和侵袭具有抑制作用,至少部分是通过抑制其靶标FSCN1的蛋白表达实现的。因此,miR-145/FSCN1可能作为NSCLC治疗的潜在靶点。