DNA甲基化介导的MicroRNA-33b下调及其在胃癌中的作用。

DNA Methylation mediated down-regulating of MicroRNA-33b and its role in gastric cancer.

作者信息

Yin Haixin, Song Peng, Su Rui, Yang Guihua, Dong Lei, Luo Min, Wang Bin, Gong Bei, Liu Changzheng, Song Wei, Wang Fang, Ma Yanni, Zhang Junwu, Wang Weibin, Yu Jia

机构信息

Department of Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences (CAMS) &Peking Union Medical College (PUMC), Beijing 100005, PR China.

Department of Surgery, The Shanxi Academy of Medical Sciences &Shanxi Dayi Hospital, Taiyuan 030032, PR China.

出版信息

Sci Rep. 2016 Jan 5;6:18824. doi: 10.1038/srep18824.

The discovery of microRNAs (miRNAs) provides a new and powerful tool for studying the mechanism, diagnosis and treatment of human cancers. Currently, down-regulation of tumor suppressive miRNAs by CpG island hypermethylation is emerging as a common hallmark of cancer. Here, we reported that the down-regulation of miR-33b was associated with pM stage of gastric cancer (GC) patients. Ectopic expression of miR-33b in HGC-27 and MGC-803 cells inhibited cell proliferation, migration and invasion, which might be due to miR-33b targeting oncogene c-Myc. Moreover, enhanced methylation level of the CpG island upstream of miR-33b in GC patients with down-regulated miR-33b was confirmed by methylation-specific PCR (MSP) amplification. Furthermore, re-introduction of miR-33b significantly suppressed tumorigenesis of GC cells in the nude mice. In conclusion, miR-33b acts as a tumor suppressor and hypermethylation of the CpG island upstream of miR-33b is responsible for its down-regulation in gastric cancer.

微小RNA（miRNA）的发现为研究人类癌症的机制、诊断和治疗提供了一种全新且强大的工具。目前，肿瘤抑制性miRNA因CpG岛高甲基化而下调正逐渐成为癌症的一个常见特征。在此，我们报告miR-33b的下调与胃癌（GC）患者的pM分期相关。在HGC-27和MGC-803细胞中异位表达miR-33b可抑制细胞增殖、迁移和侵袭，这可能是由于miR-33b靶向癌基因c-Myc所致。此外，通过甲基化特异性PCR（MSP）扩增证实，miR-33b下调的GC患者中miR-33b上游CpG岛的甲基化水平增强。此外，重新导入miR-33b可显著抑制裸鼠体内GC细胞的肿瘤发生。总之，miR-33b作为一种肿瘤抑制因子，miR-33b上游CpG岛的高甲基化是其在胃癌中下调的原因。