Green Darrell, Dalmay Tamas, Fraser William D
Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, U.K.
School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, Norfolk NR4 7TJ, U.K.
Clin Sci (Lond). 2015 Nov;129(10):863-73. doi: 10.1042/CS20150230.
Bone is increasingly viewed as an endocrine organ with key biological functions. The skeleton produces hormones and cytokines, such as FGF23 and osteocalcin, which regulate an extensive list of homoeostatic functions. Some of these functions include glucose metabolism, male fertility, blood cell production and calcium/phosphate metabolism. Many of the genes regulating these functions are specific to bone cells. Some of these genes can be wrongly expressed by other malfunctioning cells, driving the generation of disease. The miRNAs are a class of non-coding RNA molecules that are powerful regulators of gene expression by suppressing and fine-tuning target mRNAs. Expression of one such miRNA, miR-140, is ubiquitous in chondrocyte cells during embryonic bone development. Activity in cells found in the adult breast, colon and lung tissue can silence genes required for tumour suppression. The realization that the same miRNA can be both normal and detrimental, depending on the cell, tissue and time point, provides a captivating twist to the study of whole-organism functional genomics. With the recent interest in miRNAs in bone biology and RNA-based therapeutics on the horizon, we present a review on the role of miR-140 in the molecular events that govern bone formation in the embryo. Cellular pathways involving miR-140 may be reactivated or inhibited when treating skeletal injury or disorder in adulthood. These pathways may also provide a novel model system when studying cancer biology of other cells and tissues.
骨骼越来越被视为具有关键生物学功能的内分泌器官。骨骼会产生激素和细胞因子，如成纤维细胞生长因子23（FGF23）和骨钙素，它们调节一系列广泛的稳态功能。其中一些功能包括葡萄糖代谢、男性生育能力、血细胞生成以及钙/磷代谢。许多调节这些功能的基因是骨细胞特有的。其中一些基因可能会被其他功能异常的细胞错误表达，从而引发疾病。微小RNA（miRNA）是一类非编码RNA分子，通过抑制和微调靶信使核糖核酸（mRNA）来强力调节基因表达。一种这样的miRNA，即miR-140，在胚胎期骨骼发育过程中的软骨细胞中普遍表达。在成年乳腺、结肠和肺组织细胞中的活性会使肿瘤抑制所需的基因沉默。认识到同一miRNA根据细胞、组织和时间点的不同既可以是正常的也可能是有害的，这为全生物体功能基因组学的研究带来了引人入胜的转折。鉴于最近对miRNA在骨生物学中的兴趣以及基于RNA的疗法即将出现，我们对miR-140在胚胎期骨形成的分子事件中的作用进行综述。在成年期治疗骨骼损伤或疾病时，涉及miR-140的细胞途径可能会被重新激活或抑制。在研究其他细胞和组织的癌症生物学时，这些途径也可能提供一个新的模型系统。
