Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
National Key Laboratory of Science and Technology on Nano/Micro Fabrication Technology, Research Institute Micro/Nano Science and Technology, Shanghai Jiao Tong University, Shanghai, 200240, China.
Cancer Med. 2017 Jun;6(6):1331-1340. doi: 10.1002/cam4.1029. Epub 2017 Apr 24.
MicroRNA-145 (miR-145), as a tumor-suppressive miRNA, has been demonstrated down-regulated in colorectal cancer (CRC) cells, and could inhibit CRC cells growth. However, the molecular pathway in which miR-145 modulates CRC malignant transformation has not been fully revealed. Here, we reported an intense correlation between the expressions of PAK4 and miR-145 in human CRC cell lines. Transwell assay verified overexpression of miR-145, as well as knockdown of PAK4, significantly suppressed cell migration and invasion ability. The impaired migration and invasion ability of SW1116 cells was affected through the down-regulation of phosphorylation level of LIMK1 and cofilin in a PAK4-dependent manner. Collectively, we have demonstrated that miR-145 suppressed CRC migration and invasion through PAK4 pathway, which provides an attractive microRNA-based therapeutic target for CRC.
微小 RNA-145(miR-145)作为一种肿瘤抑制 miRNA,在结直肠癌细胞中表达下调,可抑制结直肠癌细胞的生长。然而,miR-145 调节结直肠癌细胞恶性转化的分子途径尚未完全揭示。在这里,我们报道了 PAK4 和 miR-145 在人结直肠癌细胞系中的表达之间存在强烈的相关性。Transwell 分析验证了 miR-145 的过表达以及 PAK4 的敲低均显著抑制了细胞迁移和侵袭能力。SW1116 细胞迁移和侵袭能力受损是通过 PAK4 依赖性方式下调 LIMK1 和丝切蛋白的磷酸化水平实现的。综上所述,我们已经证明 miR-145 通过 PAK4 通路抑制 CRC 的迁移和侵袭,这为 CRC 提供了一种有吸引力的基于 microRNA 的治疗靶点。