Micrornas Y Medicina Regenerativa

DNA AND CELL BIOLOGY Volume 26, Number 4, 2007 # Mary Ann Liebert, Inc. Pp. 257–264 DOI: 10.1089/dna.2006.0548

MicroRNAs and Regenerative Medicine
ZHAOJUAN YANG and JI WU

ABSTRACT MicroRNAs, identified only relatively recently, are regulators of gene expression with potential medical benefits. The combination of microRNAs and regenerative medicine is an emerging interdisciplinary medicalfield that can yield exciting new possibilities for clinical medicine. In this paper, we review the prospects of microRNAs as future therapies in regenerative medicine. Recently, researchers have demonstrated the crucial roles of microRNAs, not only in the differentiation and proliferation of stem cells, which have a key function in the regeneration and transplantation of organs, but also inoncogenesis. Several lines of indirect evidence show that the initiation and maintenance of cancer stem cells might also be under the control of microRNAs. Further, microRNAs have been indicated to be involved in diverse biological processes, suggesting the potential role of these molecules in the treatment of diseases.

INTRODUCTION
ICRORNAS ARE AN ABUNDANT CLASS of short, noncoding RNA molecules,approximately 22 nucleotides (nt) in length, which regulate gene expression through inhibiting the ´ translation of target genes (Olsen and Ambros, 1999; Hutvagner and Zamore, 2002; Zeng et al., 2003; Bartel, 2004; Yang and Wu, 2006). The first microRNA was identified little more than a decade ago (Lee et al., 1993). Recently, research on microRNAs is at the center stage of many biological areas.MicroRNAs can silence the expression of target mRNAs by binding to their complementary sequences within the 30 untranslated region (30 UTR). Just 1 microRNA molecule can regulate hundreds of distinct mRNA targets (Lewis et al., 2005). In the human genome, it is possible that the majority of human genes are under the control of microRNAs. Therefore, it is not surprising that microRNAs might participate ina wide range of biological processes. Regenerative medicine is an emerging interdisciplinary field whose goal is to repair, replace, or regenerate cells, tissues, or organs that are lost or damaged due to disease, injury, or ageing. This approach is very different from the more conventional approach of administering chemically based drugs. Proteins, cDNA, genes, cells, and tissues are all used asregenerative medicines. Recent advances in this field have been influenced by our understanding in multiple areas, including tissue engineering, stem cell biology, tissue turnover and replacement in adult mammals, and embryonic development (Alonso and Fuchs,

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2003; Harada and Rodan, 2003; Dor et al., 2004; Leor et al., 2005; Radtke and Clevers, 2005; Sage et al., 2005). Regenerative medicinesare classified into 4 broad types based on their characteristics: human substances (proteins and genes), cells and tissues (a form of tissue engineering), embryonic stem (ES) cells, and novel materials (Haseltine, 2003). Some recent papers have reported abnormal expression of microRNAs in various forms of cancer, suggesting the role of microRNAs in oncogenesis, and some of these seem to have thecharacteristics of stem cell microRNAs (Takamizawa et al., 2004; Cimmino et al., 2005; Eis et al., 2005; Felli et al., 2005; He et al., 2005). Some researchers now consider that cancer stem cells may contribute to the development and transformation of human cancers (Lessard and Sauvageau, 2003; Guo et al., 2006). To exactly determine whether or not the initiation and maintenance of cancer stem cellsare regulated by microRNAs will require further studies. In this review, we summarize some indirect evidence to support the concept that microRNAs control these processes. Moreover, there is increasing evidence of the essential role of microRNAs in the self-renewal and differentiation of stem cells, including ES cells, suggesting the prospect of using microRNAs in organ transplantation and...