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miR-27a 通过靶向 Sprouty2 调节胰腺癌细胞的生长、集落形成和迁移。

miR-27a regulates the growth, colony formation and migration of pancreatic cancer cells by targeting Sprouty2.

机构信息

Department of Pathology, Peking Union Medical College Hospital, People's Republic of China.

出版信息

Cancer Lett. 2010 Dec 8;298(2):150-8. doi: 10.1016/j.canlet.2010.06.012. Epub 2010 Jul 17.

DOI:10.1016/j.canlet.2010.06.012
PMID:20638779
Abstract

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.

摘要

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。

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