Abstract

The dysregulation of microRNA expression is significantly associated with the initiation and development of CRC. miR-124 is markedly downregulated in colorectal cancer. In the present study, the effects of methylation, over expression and downregulation of miR-124 and its target gene DNMT3B on the proliferation, migration and invasion of colorectal cell line were investigated. The promoter methylation status of miR-124 in the CRC was investigated by methylation specific PCR (MSP). The potential role of miR-124 expression in CRC cells was investigated using the demethylation reagent 5-Aza-CdR and transfection of miR-124 mimic/antimir. MSP revealed that miR-124 promoter region was hypermethylated, result in its significant downregulation in tumour tissues. We showed miR-124 expression was upregulated following 5-AZA-CdR treatment. Transfected Hct-116 cell line with miR-124 leads to decreased DNMT3B expression, cell proliferation, migration and invasion of HCT-116. In conclusion, our data indicate that miR-124 suppress colorectal cancer proliferation, migration and invasion through downregulating DNMT3B level.

摘要

microRNA表达的失调与CRC的发生和发展显着相关。miR-124 在结直肠癌中显着下调。本研究探讨了miR-124及其靶基因DNMT3B甲基化、过表达和下调对结直肠细胞增殖、迁移和侵袭的影响。通过甲基化特异性PCR（MSP）研究CRC中miR-124的启动子甲基化状态。使用去甲基化试剂 5-Aza-CdR 和转染 miR-124 mimic/antimir 研究了 miR-124 表达在 CRC 细胞中的潜在作用。MSP 显示 miR-124 启动子区域被高甲基化，导致其在肿瘤组织中显着下调。我们显示 miR-124 表达在 5-AZA-CdR 处理后上调。用 miR-124 转染的 Hct-116 细胞系导致 HCT-116 的 DNMT3B 表达、细胞增殖、迁移和侵袭降低。总之，我们的数据表明 miR-124 通过下调 DNMT3B 水平抑制结直肠癌的增殖、迁移和侵袭。