Department of Pathology, Peking Union Medical College Hospital, People's Republic of China.
Cancer Lett. 2010 Dec 8;298(2):150-8. doi: 10.1016/j.canlet.2010.06.012. Epub 2010 Jul 17.
MicroRNAs are short regulatory RNAs. A growing body of data implicates altered miRNA participate in the development of cancers and miR-27a is abnormally upregulated in several types of cancers identified as an oncogene. Although overexpressed in pancreatic adenocarcinoma, the oncogenic role of miR-27a has not yet been reported. In this study, we showed that inhibition of miR-27a suppressed the growth, colony formation and migration of pancreatic cancer cells. By using a reporter-screening assay, we discovered that the 3'UTR of Sprouty2 (Spry2) carried a putative miR-27a binding site. Furthermore, the Spry2 protein, which has a low expression level in pancreatic adenocarcinoma, was upregulated by transfection with a miR-27a inhibitor. The data reported here are the first to indicate that miR-27a plays an oncogenic role by targeting Spry2 and modulating the malignant, biological behavior of pancreatic cancer cells. This suggests the potential for miR-27a to be used as a target in the diagnosis and treatment of pancreatic adenocarcinoma.
微小 RNA 是短链调控 RNA。越来越多的数据表明,异常表达的 miRNA 参与了癌症的发生,miR-27a 在几种已被鉴定为癌基因的癌症中异常上调。尽管在胰腺腺癌中过度表达,但 miR-27a 的致癌作用尚未被报道。在这项研究中,我们发现抑制 miR-27a 可抑制胰腺癌细胞的生长、集落形成和迁移。通过使用报告基因筛选试验,我们发现 Sprouty2 (Spry2) 的 3'UTR 携带有一个假定的 miR-27a 结合位点。此外,用 miR-27a 抑制剂转染可上调胰腺腺癌中低表达的 Spry2 蛋白。这里报告的数据首次表明,miR-27a 通过靶向 Spry2 并调节胰腺癌细胞的恶性生物学行为发挥致癌作用。这表明 miR-27a 有可能成为胰腺腺癌诊断和治疗的靶点。