Liu Liwei, Zhang Chao, Li Xiyu, Sun Wenjia, Qin Shenghui, Qin Lingzhi, Wang Xi
Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Oncotarget. 2017 Jul 25;8(38):63764-63779. doi: 10.18632/oncotarget.19541. eCollection 2017 Sep 8.
microRNA (miRNA) dysregulation is frequently observed in colon cancer. Previous studies found that miR-223 is upregulated in colon cancer and functions as an oncogene. Conversely, p120 is often downregulated or even absent in colon cancer, and is a likely tumor suppressor. The present study showed that increased miR-223 and decreased p120 levels are associated with colon cancer malignancy, and p120 expression is negatively correlated with miR-223 expression. A dual luciferase reporter assay showed that miR-223 directly targets p120. miR-223 upregulation in a colon cancer cell line upregulated c-Myc, cyclinD1, MMP7, and vimentin expression, downregulated E-cadherin, increased nuclear expression of β-catenin, and enhanced RhoA activation. We suggest miR-223 may promote colon cancer cell invasion and metastasis by downregulating p120, thereby reducing intercellular adhesion, promoting RhoA activity, and activating β-catenin signaling. Thus miR-223 functions as an oncogene in colon cancer and may be a potential diagnostic and therapeutic target for anti-colon cancer treatment.
微小RNA（miRNA）失调在结肠癌中经常被观察到。先前的研究发现，miR-223在结肠癌中上调并发挥癌基因的作用。相反，p120在结肠癌中常常下调甚至缺失，并且可能是一种肿瘤抑制因子。本研究表明，miR-223水平升高和p120水平降低与结肠癌的恶性程度相关，并且p120表达与miR-223表达呈负相关。双荧光素酶报告基因检测表明，miR-223直接靶向p120。在结肠癌细胞系中上调miR-223会使c-Myc、细胞周期蛋白D1、基质金属蛋白酶7和波形蛋白的表达上调，使E-钙黏蛋白下调，β-连环蛋白的核表达增加，并增强RhoA激活。我们认为，miR-223可能通过下调p120来促进结肠癌细胞的侵袭和转移，从而减少细胞间黏附，促进RhoA活性并激活β-连环蛋白信号传导。因此，miR-223在结肠癌中发挥癌基因的作用，并且可能是抗结肠癌治疗的潜在诊断和治疗靶点。
