Cui Mingfu, Chen Mingyan, Shen Zhaoming, Wang Ruijie, Fang Xuedong, Song Bin
Department of Gastrointestinal and Colorectal Surgery, China-Japan Union Hospital, Jilin University, Changchun, China.
Department of General Surgery, General Hospital of FAW (The Fourth Hospital of Jilin University), Changchun, China.
J Cell Biochem. 2019 May;120(5):6926-6936. doi: 10.1002/jcb.27630. Epub 2019 Jan 16.
Emerging evidence has shown that the long noncoding RNA urothelial carcinoma-associated 1 (UCA1) plays a tumor-promoting role in colorectal cancer, while miR-28-5p shows tumor-inhibitory activity in several tumor types. However, the mechanisms both of these in colon cancer progression are still unknown. In this work, the detailed roles and mechanisms of UCA1 and its target genes in colon cancer were studied. The results showed that UCA1 was upregulated in colon cancer tissues when compared with the adjacent nonhumorous tissues, as well as in the various colon cancer cell lines, but the expression of miR-28-5p showed an opposite trend. Furthermore, a high UCA1 level in colon cancer tissues is positively associated with the tumor size and advanced tumor stages. Functional assays revealed that both UCA1 knockdown and miR-28-5p overexpression could inhibit colon cancer cell growth and migration. Further mechanistic studies indicated that UCA1 knockdown played tumor suppressive roles in SW480 and HT116 cells through binding with miR-28-5p. We also, for the first time, identified HOXB3 as the target gene of miR-28-5p and that HOXB3 overexpression could mediate the functions of UCA1 in cell proliferation and migration of colon cancer cells. In conclusion, our data provided evidence for the regulatory network of UCA1/miR-28-5p/HOXB3 in colon cancer, suggesting that UCA1, miR-28-5p, and HOXB3 are the potential targets for colon cancer therapy.
新出现的证据表明,长链非编码RNA尿路上皮癌相关1(UCA1)在结直肠癌中发挥促肿瘤作用,而miR-28-5p在多种肿瘤类型中表现出肿瘤抑制活性。然而,这两者在结肠癌进展中的机制仍不清楚。在这项研究中,我们研究了UCA1及其靶基因在结肠癌中的具体作用和机制。结果显示,与相邻的非肿瘤组织相比,UCA1在结肠癌组织中以及在各种结肠癌细胞系中均上调,但miR-28-5p的表达呈现相反趋势。此外,结肠癌组织中高UCA1水平与肿瘤大小和晚期肿瘤分期呈正相关。功能试验表明,敲低UCA1和过表达miR-28-5p均可抑制结肠癌细胞的生长和迁移。进一步的机制研究表明,敲低UCA1通过与miR-28-5p结合在SW480和HT116细胞中发挥肿瘤抑制作用。我们还首次确定HOXB3是miR-28-5p的靶基因,并且HOXB3过表达可介导UCA1在结肠癌细胞增殖和迁移中的功能。总之,我们的数据为UCA1/miR-28-5p/HOXB3在结肠癌中的调控网络提供了证据,表明UCA1、miR-28-5p和HOXB3是结肠癌治疗的潜在靶点。