Department of Gastrointestinal Surgery, Affiliated Hospital of Jining Medical College, Jining, P.R. China.
Department of Medical Ultrasonography, Affiliated Hospital of Jining Medical College, Jining, P.R. China.
Oncol Res. 2019 Mar 29;27(4):399-406. doi: 10.3727/096504018X15179675206495. Epub 2018 Feb 9.
Colon cancer is one of the most common cancers in the world. Epithelial-to-mesenchymal transition (EMT) is a crucial step in tumor progression and is also involved in the acquisition of stem cell-like properties. Some miRNAs have been shown to function as either tumor suppressors or oncogenes in colon cancer. Here we investigated the role of miR-147 in the regulation of the stem cell-like traits of colon cancer cells. We observed that miR-147 was downregulated in several colon cancer cell lines, and overexpressed miR-147 decreased the expression of cancer stem cell (CSC) markers OCT4, SOX2, and NANOG in the colon cancer cell lines HCT116 and SW480. Overexpressed miR-147 inhibited EMT by increasing the expression of epithelial markers E-cadherin and α-catenin while decreasing the expression of mesenchymal markers fibronectin and vimentin. Moreover, activation of EMT by TGF-β1 treatment significantly counteracted the inhibitive effect of miR-147 on the expression of CSC markers OCT4, SOX2, and NANOG, supporting the idea that overexpressing miR-147 inhibited stem cell-like traits by suppressing EMT in colon cancer. In addition, we found that overexpressed miR-147 downregulated the expression of β-catenin, c-myc, and survivin, which were related to the Wnt/β-catenin pathway. Moreover, treatment of miR-147 mimic-transfected cells with the Wnt/β-catenin pathway activator LiCl attenuated the inhibitive effect of the miR-147 mimic on the EMT and stem cell-like traits of colon cancer cells, indicating that ectopic expression of miR-147 inhibited stem cell-like traits in colon cancer cells by suppressing EMT via the Wnt/β-catenin pathway. In summary, our present study highlighted the crucial role of miR-147 in the inhibition of the stem cell-like traits of colon cancer cells and indicated that miR-147 could be a promising therapeutic target for colon cancer treatment.
结肠癌是世界上最常见的癌症之一。上皮间质转化（EMT）是肿瘤进展的关键步骤，也参与了获得干细胞样特性。一些 miRNA 已被证明在结肠癌中作为肿瘤抑制因子或癌基因发挥作用。在这里，我们研究了 miR-147 在调节结肠癌细胞的干细胞样特征中的作用。我们观察到 miR-147 在几种结肠癌细胞系中下调，过表达 miR-147 降低了结肠癌细胞系 HCT116 和 SW480 中癌症干细胞（CSC）标志物 OCT4、SOX2 和 NANOG 的表达。过表达 miR-147 通过增加上皮标志物 E-钙粘蛋白和α-连环蛋白的表达，同时降低间充质标志物纤连蛋白和波形蛋白的表达，抑制 EMT。此外，TGF-β1 处理诱导的 EMT 显著抵消了 miR-147 对 CSC 标志物 OCT4、SOX2 和 NANOG 表达的抑制作用，支持了过表达 miR-147 通过抑制 EMT 抑制结肠癌中干细胞样特征的观点。此外，我们发现过表达 miR-147 下调了与 Wnt/β-连环蛋白通路相关的β-连环蛋白、c-myc 和 survivin 的表达。此外，用 Wnt/β-连环蛋白通路激活剂 LiCl 处理转染 miR-147 模拟物的细胞减弱了 miR-147 模拟物对结肠癌细胞 EMT 和干细胞样特征的抑制作用，表明过表达 miR-147 通过抑制 EMT 抑制结肠癌中干细胞样特征通过 Wnt/β-连环蛋白通路。总之，我们的研究强调了 miR-147 在抑制结肠癌细胞的干细胞样特征中的关键作用，并表明 miR-147 可能是结肠癌治疗的有前途的治疗靶点。
