Cancer Cell：与肌肉癌相关特殊分子

美国科学家近日研究发现，一种与白血病和肺癌有关的分子，对于肌修复和一种肌肉癌同样重要。相关论文发表在《癌细胞》（Cancer Cell）杂志上。
俄亥俄州立大学研究人员Denis C. Guttridge和同事发现，肌细胞需要这一称为miR-29（一种小分子RNA）的分子以达到成熟状态，而来自横纹肌肉瘤（rhabdomyosarcoma）的细胞中几乎不存在这种分子，横纹肌肉瘤是由未成熟肌细胞增殖导致的一种癌症。
研究人员发现，miR-29基因的活性被NF-κB蛋白“沉默”。横纹肌肉瘤细胞中含有高浓度的这种蛋白，使得miR-29的作用被切断，从而阻止了肌肉祖细胞的成熟。
人工提升横纹肌肉瘤细胞中miR-29的水平会将癌细胞的增殖减半，并促使它们开始成熟，减慢了肿瘤生长。
科学家表示，此次的研究与众不同，它阐明了小分子RNA自身如何被调控。Guttridge说：“研究表明miR-29、肌肉发育和横纹肌肉瘤之间存在联系。这一发现为我们提供了关于肌修复和发育以及横纹肌肉瘤更深入的理解，有可能由此产生治疗该病及其它肌肉疾病的新方法。”（生物谷Bioon.com）
生物谷推荐原始出处：
Cancer Cell，Volume 14, Issue 5, 369-381，Huating Wang，Denis C. Guttridge
NF-κBYY1miR-29 Regulatory Circuitry in Skeletal Myogenesis and Rhabdomyosarcoma
Huating Wang1,Ramiro Garzon1,Hao Sun1,Katherine J. Ladner1,Ravi Singh2,Jason Dahlman1,Alfred Cheng1,4,Brett M. Hall2,Stephen J. Qualman2,Dawn S. Chandler2,Carlo M. Croce1,3andDenis C. Guttridge1,3,,
1 Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA2 Department of Pediatrics, Nationwide Children's Hospital, The Ohio State University, Columbus, OH 43210, USA3 The Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA4 Present address: Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong
Studies support the importance of microRNAs in physiological and pathological processes. Here we describe the regulation and function of miR-29 in myogenesis and rhabdomyosarcoma (RMS). Results demonstrate that in myoblasts, miR-29 is repressed by NF-κB acting through YY1 and the Polycomb group. During myogenesis, NF-κB and YY1 downregulation causes derepression of miR-29, which in turn accelerates differentiation by targeting its repressor YY1. However, in RMS cells and primary tumors that possess impaired differentiation, miR-29 is epigenetically silenced by an activated NF-κBYY1 pathway. Reconstitution of miR-29 in RMS in mice inhibits tumor growth and stimulates differentiation, suggesting that miR-29 acts as a tumor suppressor through its promyogenic function. Together, these results identify a NF-κBYY1miR-29 regulatory circuit whose disruption may contribute to RMS.