MicroRNAs (miRNAs) are gene modulators essential for biological processes. However, the precise functions of miRNAs in growth and development of colon cancer are still elusive. To clarify their role, here we analyzed a miRNA microarray of colon cancer. MiR-182-5p was found markedly downregulated in colon cancer tissues and cells, and strongly correlated with pathological stage, differentiation, and lymphatic metastasis. In vitro, miR-182-5p overexpression repressed colon cancer cell proliferation, colony formation, migration, and invasion, and triggered G1 arrest and apoptosis. MiR-182-5p overexpression also downregulated vascular endothelial growth factor (VEGF)-C and inhibited the activity of a luciferase reporter containing the VEGF-C 3′-untranslated region. Moreover, miR-182-5p overexpression in colon cancer cells and human umbilical vein endothelial cells (HUVECs) downregulated VEGF-A as well as VEGF receptor (VEGFR)-2 and VEGFR-3, thereby inhibiting the phosphorylation of ERK and AKT. In vivo, miR-182-5p overexpression strikingly suppressed oncogenicity of SW620 cells as well as angiogenesis and lymphangiogenesis of xenograft tumors in nude mice. These data indicate that miR-182-5p regulates colon cancer tumorigenesis partially through modulating angiogenesis and lymphangiogenesis by targeting VEGF-C, and inhibiting ERK and AKT signaling pathways.

微小RNA（miRNA）是生物学过程必不可少的基因调节剂。但是，miRNA在结肠癌的生长和发育中的确切功能仍然难以捉摸。为了阐明其作用，在这里我们分析了结肠癌的miRNA芯片。发现MiR-182-5p在结肠癌组织和细胞中明显下调，并且与病理分期，分化和淋巴转移密切相关。在体外，miR-182-5p过表达抑制结肠癌细胞的增殖，集落形成，迁移和侵袭，并触发G1阻滞和凋亡。MiR-182-5p过表达还下调了血管内皮生长因子（VEGF）-C，并抑制了包含VEGF-C 3'-非翻译区的荧光素酶报道分子的活性。此外，miR-182-5p在结肠癌细胞和人脐静脉内皮细胞（HUVEC）中的过表达下调VEGF-A以及VEGF受体（VEGFR）-2和VEGFR-3，从而抑制ERK和AKT的磷酸化。在体内，miR-182-5p过表达显着抑制SW620细胞的致癌性以及裸鼠异种移植肿瘤的血管生成和淋巴管生成。这些数据表明，miR-182-5p通过靶向VEGF-C并抑制ERK和AKT信号通路，通过调节血管生成和淋巴管生成来部分调节结肠癌的肿瘤发生。miR-182-5p过表达显着抑制SW620细胞的致癌性以及裸鼠异种移植肿瘤的血管生成和淋巴管生成。这些数据表明，miR-182-5p通过靶向VEGF-C并抑制ERK和AKT信号通路，通过调节血管生成和淋巴管生成来部分调节结肠癌的肿瘤发生。miR-182-5p过表达显着抑制SW620细胞的致癌性以及裸鼠异种移植肿瘤的血管生成和淋巴管生成。这些数据表明，miR-182-5p通过靶向VEGF-C并抑制ERK和AKT信号通路，通过调节血管生成和淋巴管生成来部分调节结肠癌的肿瘤发生。