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NATURE REPRINT COLLECTION microRNAs

NATURE REPRINT COLLECTION microRNAs

2012/02/09 16:45:04

Sponsor foreword

In this collection we highlight key publications that have advanced the understanding of microRNA biology and effects on gene regulation. Importantly, as the field has matured and the first microRNA-based drug achieved human proof-of-concept, these papers further link microRNA dysregulation to disease pathogenesis and provide strong validation of microRNAs as promising targets for therapeutics.

    Several microRNAs clearly have a role in metabolic pathways. For example, miR-33a/b inhibition in non-human primates raises plasma HDL cholesterol, the ‘good’ cholesterol, and lowers triglycerides (Rayner et al. 2011, p2). Additionally, miR-103/107 can regulate insulin sensitivity and may represent a new target for the treatment of diabetes and obesity (Trajkovski et al. 2011, p11).

    Other microRNAs have been linked to developmental processes such as vascular development and bone formation. As an example, miR-132 can facilitate angiogenesis (Anand et al. 2010, p21) and the hemizygous germline deletion of the miR-17-92 cluster causes skeletal and growth defects in humans (Pontual et al. 2011, p16).

    Targeting oncogenic microRNAs has emerged as a promising strategy for cancer therapy. For example, tumors can become addicted to oncogenic microRNAs, termed oncomiRs, as shown in an in vivo model of microRNA-21 induced B-cell lymphoma (Medina et al. 2010, p6). Inhibition of miR-182, a microRNA frequently overexpressed in several cancer types, repressed metastasis in a mouse model of melanoma liver metastasis (Huynh et al. 2011, p41), and inhibition of miR-10b inhibits metastasis in a mouse breast cancer model (Ma et al. 2010, p27). Furthermore, miR-380-5p represses the tumor suppressor p53 and was associated with poor outcomes in neuroblastoma (Swarbrick et al. 2010, p34).

    We are pleased to bring you this collection highlighting the exciting developments around the potential for creating powerful first-in-class medicines targeting microRNAs. Kleanthis G. Xanthopoulos, Ph.D.

Regulus Therapeutics President and CEO

 

**Content: **

  • 2 Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides. Rayner, K. J. et al. Nature 478, 404–407 (2011)

  • 6 OncomiR addiction in an in vivo model of microRNA-21-induced pre-B-cell lymphoma. Medina, P. P., Nolde, M. & Slack, F. J. Nature 467, 86–90 (2010)

  • 11 MicroRNAs 103 and 107 regulate insulin sensitivity. Trajkovski, M. et al. Nature 474, 649–653 (2011)

  • 16 Germline deletion of the miR-17~92 cluster causes skeletal and growth defects in humans. de Pontual, L. et al. Nature Genet. 43, 1026–1030 (2011)

  • 21 MicroRNA-132-mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis. Anand, S. et al. Nature Med. 16, 909–914 (2010)

  • 27 Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Ma, L. et al. Nature Biotechnol. 28, 341–347 (2010)

  • 34 miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastoma. Swarbrick, A. et al. Nature Med. 16, 1134–1140 (2010)

  • 41 Efficient in vivo microRNA targeting of liver metastasis. Huynh, C. et al. Oncogene 30, 1481–1488 (2011)

nature-miRNA.pdf