Zhu Mingchen, Xu Yijun, Ge Mengyuan, Gui Zhen, Yan Feng
Department of Clinical Laboratory, Jiangsu Cancer Hospital & Nanjing Medical University Cancer Hospital, Nanjing, China.
Department of Pharmacology, Nanjing Medical University, Nanjing, China.
Cancer Sci. 2015 Jul;106(7):833-9. doi: 10.1111/cas.12689. Epub 2015 Jun 17.
The UHRF1 protein is pivotal for DNA methylation and heterochromatin formation, leading to decreased expressions of tumor suppressor genes and contributing to tumorigenesis. However, the factors that modulate UHRF1 expression in colorectal cancer (CRC) remain unclear. Here we showed that, compared with corresponding normal tissues, UHRF1 was upregulated and microRNA-9 (miR-9) was downregulated in CRC tissues. The expression of UHRF1 was inversely correlated with overall survival rates of patients with CRC. Overexpression of miR-9 in CRC cell lines significantly attenuated CRC cell proliferation and promoted cell apoptosis. The expression of UHRF1 was markedly reduced in pre-miR-9 transfected CRC cells. Using luciferase reporter assay, we confirmed that miR-9 was a direct upstream regulator of UHRF1. Finally, analysis of miR-9 and UHRF1 levels in human CRC tissues revealed that expression of miR-9 was inversely correlated with UHRF1 expression. Collectively, our results offer in vitro validation of the concept that miR-9 could repress the expression of UHRF1, and function as a tumor-suppressive microRNA in CRC. It may serve as a prognostic and therapeutic marker for CRC.
UHRF1蛋白对于DNA甲基化和异染色质形成至关重要，导致肿瘤抑制基因表达降低并促进肿瘤发生。然而，调节结直肠癌（CRC）中UHRF1表达的因素仍不清楚。在此我们表明，与相应的正常组织相比，CRC组织中UHRF1上调而微小RNA-9（miR-9）下调。UHRF1的表达与CRC患者的总生存率呈负相关。在CRC细胞系中过表达miR-9可显著减弱CRC细胞增殖并促进细胞凋亡。在转染pre-miR-9的CRC细胞中，UHRF1的表达明显降低。使用荧光素酶报告基因检测，我们证实miR-9是UHRF1的直接上游调节因子。最后，对人CRC组织中miR-9和UHRF1水平的分析表明，miR-9的表达与UHRF1的表达呈负相关。总体而言，我们的结果为miR-9可抑制UHRF1表达这一概念提供了体外验证，并且miR-9在CRC中作为一种肿瘤抑制性微小RNA发挥作用。它可能作为CRC的预后和治疗标志物。
