Oncogene：小miRNA 抑癌大显身手

　　

生物通报道，来自耶鲁大学，Mirna Therapeutics, Inc.的科学家在最近一期的Oncogene上发表了microRNA治疗肺癌的研究性进展文章Regression of murine lung tumors by the let-7 microRNA。

 

这篇文章首次展示了microRNA对癌症治疗方面的影响，为未来microRNA在癌症临床治疗方面发挥作用奠定了基础。

 

文章通讯作者，耶鲁大学癌症研究中心教授Franck Slack介绍道：这是我们首次获得microRNA在肺癌治疗方面的积极效果。

 

microRNA（miRNA）为一类大小约22个核苷酸的非编码小分子RNA,它们能通过与靶mRNA的3′UTR（非编码区）完全互补导致mRNA降解,或不完全互补结合阻断mRNA翻译。

miRNA let一7位于人9号染色体。

 

研究小组以患有非小细胞肺癌的小鼠为研究模型，将一种名为let-7的microRNA导入小鼠体内，结果发现let-7可有效抑制肿瘤的发展。

 

let-7功能试验以剔除let-7来进行，结果发现缺失let-7可促进小鼠肺癌的发生。这就证实let-7是一种肿瘤抑制因子。

 

尽管接受let-7治疗，小鼠的肿瘤没有消失，但是66%的都在缩小。研究小组将进一步研究let-7对癌症的治疗功效，他们希望将microRNA let-7与化疗及放射性疗法结合起来。

 

 

Let-7 treated lung shows regression of cancer tumors. (Credit: Image courtesy of Yale University)

 

Slack表示，let-7的缺失可能导致多种癌症的发生，这证明let-7在人类癌症的发展过程中起重要的作用。我们希望能评估let-7对其他多种癌症的治疗效果。期盼let-7可在多种癌症中发挥功效。

（生物通 小茜）

生物通推荐原文检索

Oncogene advance online publication 7 December 2009; doi: 10.1038/onc.2009.445

 

Regression of murine lung tumors by the let-7 microRNA

P Trang1,2,6, P P Medina1,6, J F Wiggins3, L Ruffino3, K Kelnar3, M Omotola3, R Homer4,5, D Brown3, A G Bader3, J B Weidhaas2 and F J Slack1

 

1Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA

2Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA

3Mirna Therapeutics Inc. (a subsidiary of Asuragen Inc.), Austin, TX, USA

4Department of Pathology, Yale University School of Medicine, New Haven, CT, USA

5Department of Pathology and Laboratory Medicine Service, VA Connecticut Healthcare System, West Haven, CT, USA

Correspondence: Dr AG Bader, Mirna Therapeutics, Inc. (a subsidiary of Asuragen Inc.), 2150 Woodward Street, Austin, TX, USA. E-mail: [e-mail]; Dr JB Weidhaas, Department of Therapeutic Radiology, Yale University School of Medicine, PO Box 208040, New Haven, CT 06520, USA. E-mail: [e-mail]; Dr FJ Slack, Department of Molecular, Cellular and, Developmental Biology, KBT 936, Yale University, PO Box 208103, 266 Whitney Avenue, New Haven, CT 06520, USA. E-mail: [e-mail]

6These authors contributed equally to this work.

 

Received 20 July 2009; Revised 26 October 2009; Accepted 3 November 2009; Published online 7 December 2009.

 

【Abstract】

MicroRNAs (miRNAs) have recently emerged as an important new class of cellular regulators that control various cellular processes and are implicated in human diseases, including cancer. Here, we show that loss of let-7 function enhances lung tumor formation in vivo, strongly supporting the hypothesis that let-7 is a tumor suppressor. Moreover, we report that exogenous delivery of let-7 to established tumors in mouse models of non-small-cell lung cancer (NSCLC) significantly reduces the tumor burden. These results demonstrate the therapeutic potential of let-7 in NSCLC and point to miRNA replacement therapy as a promising approach in cancer treatment.