Li Yong-Chao, Li Chang-Feng, Chen Li-Bo, Li Dan-Dan, Yang Lei, Jin Jing-Peng, Zhang Bin
Department of Gastrointestinal Surgery, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China.
Department of Endoscopy Center, China-Japan Union Hospital of Jilin University, Changchun, People's Republic of China.
Onco Targets Ther. 2015 Oct 20;8:2981-8. doi: 10.2147/OTT.S89459. eCollection 2015.
MicroRNAs (miRNAs) have emerged as important regulators of cancer-cell biological processes. Previous studies have shown that miR-766 plays an important role in a variety of biological processes in various human cancers. However, the underlying mechanism of miR-766 in colorectal cancer (CRC) cells remains unclear. In this study, we investigated miR-766's role in CRC cell proliferation. Polymerase chain reaction results showed that miR-766 expression was significantly upregulated in CRC tissues and cells. Ectopic expression of miR-766 promoted cell growth and anchorage-independent growth in CRC cells. Bioinformatic analysis predicted SOX6, a potential target of miR-766, acting as a tumor suppressor. Luciferase reporter assay results demonstrated that miR-766 directly bound to the 3'-untranslated region of SOX6. Overexpression of miR-766 suppressed SOX6 expression, resulting in the downregulation of p21 and upregulation of cyclin D1. In a further experiment, SOX6-silenced SW480 cells transfected with miR-766 promoted cell growth, suggesting that downregulation of SOX6 was required for miR-766-induced CRC cell proliferation. Taken together, these results suggested that miR-766 represents an onco-miRNA and participates in the development of CRC by modulating SOX6 expression.
微小RNA(miRNA)已成为癌细胞生物学过程的重要调节因子。先前的研究表明,miR-766在各种人类癌症的多种生物学过程中发挥重要作用。然而,miR-766在结直肠癌(CRC)细胞中的潜在机制仍不清楚。在本研究中,我们调查了miR-766在CRC细胞增殖中的作用。聚合酶链反应结果显示,miR-766在CRC组织和细胞中的表达显著上调。miR-766的异位表达促进了CRC细胞的生长和非锚定依赖性生长。生物信息学分析预测SOX6是miR-766的潜在靶标,作为一种肿瘤抑制因子。荧光素酶报告基因检测结果表明,miR-766直接与SOX6的3'-非翻译区结合。miR-766的过表达抑制了SOX6的表达,导致p21下调和细胞周期蛋白D1上调。在进一步的实验中,用miR-766转染的SOX6沉默的SW480细胞促进了细胞生长,表明miR-766诱导的CRC细胞增殖需要SOX6的下调。综上所述,这些结果表明miR-766是一种致癌miRNA,并通过调节SOX6的表达参与CRC的发展。