Department of General Surgery, Second Affiliated Hospital of Harbin Medical University, Hei LongJiang, Harbin, China.
Eur J Cancer. 2011 Nov;47(17):2552-9. doi: 10.1016/j.ejca.2011.05.021. Epub 2011 Jun 16.
MicroRNAs (miRNAs) are a recently discovered class of small non-coding RNAs that regulate gene expression and may contribute to the development and progression of many cancers. In this study, our goal was to investigate the regulation of miR-429 in gastric cancer and explored the mechanism/s by which it influenced pathogenesis of gastric cancer.
We used real-time reverse transcriptase-polymerase chain reaction to quantify the expression level of miR-429 in 52 gastric cancer tissues and their paracancerous tissues. Bioinformatics was used to predict downstream target genes of miR-429. SGC-7901 gastric cancer cells were transfected with miR-429 mimics and endogenous c-myc expression was detected by western blots. We performed functional assays using the 3'UTR of the c-myc gene as a miR-429 target in a luciferase reporter assay system.
We showed that miR-429 was downregulated in human gastric carcinoma tissue and in SGC-7901 cells. Cell viability, proliferation and attachment were inhibited in miR-429-transfected cells. miR-429 significantly downregulated endogenous c-myc expression in SGC-7901 cells. Action of miR/429 on c-myc 3'UTR was confirmed. The levels of miR-429 in tumour tissue of patients with lymph node metastasis were significantly lower than in those without lymph node metastasis.
Our results suggested that miR-429 played a role in the pathogenesis of gastric carcinoma and may function as a recessive cancer gene. c-myc is an important miR-429 target gene.
微小 RNA(miRNA)是一类新发现的小非编码 RNA,可调节基因表达,可能有助于多种癌症的发生和发展。本研究旨在探讨 miR-429 在胃癌中的调控作用,并研究其影响胃癌发病机制的机制。
我们使用实时逆转录-聚合酶链反应定量检测 52 例胃癌组织及其癌旁组织中 miR-429 的表达水平。生物信息学用于预测 miR-429 的下游靶基因。用 miR-429 模拟物转染 SGC-7901 胃癌细胞,用 Western blot 检测内源性 c-myc 表达。我们在荧光素酶报告基因检测系统中,将 c-myc 基因的 3'UTR 作为 miR-429 的靶基因进行功能测定。
我们表明 miR-429 在人胃癌组织和 SGC-7901 细胞中下调。转染 miR-429 的细胞的细胞活力、增殖和附着受到抑制。miR-429 显著下调 SGC-7901 细胞中的内源性 c-myc 表达。miR/429 对 c-myc 3'UTR 的作用得到证实。有淋巴结转移的患者肿瘤组织中的 miR-429 水平明显低于无淋巴结转移的患者。
我们的研究结果表明,miR-429 在胃癌的发病机制中起作用,可能作为隐性癌基因发挥作用。c-myc 是 miR-429 的一个重要靶基因。