MicroRNA-Dependent Control of the Cardiac Fibroblast Secretome

Abstract

Biological discovery is very much dependent on technological innovation, and often the reverse is true too. Up to relatively recently, research has had to adopt a reductionist approach to biological discovery, that is, one focusing on a single gene, protein, pathway, etc, because of the constraints imposed by the available tools of discovery. Nowadays, the increasingly sophisticated nature of our current tools and the advances made in computing science and information technology are ushering us into a new era, one of systems biology1 and, possibly, personalized medicine.2 Article, see p 1138 MicroRNA (miRNA), a family of short noncoding RNAs that inhibit gene expression at the post-transcriptional level by targeting mRNA for degradation or repression, is now understood to be a major regulatory element of biological systems.3 The uncovering of miRNA-mediated regulation is greatly advancing our understanding of how biological processes are controlled and has fuelled the promise of improved therapeutics for difficult-to-treat, and even currently untreatable, pathologies. But, because of the very nature of how miRNAs work, that is, as finetuners within a regulatory network, studying them not only individually, but also isolated from the rest of the cellular regulatory apparatus cannot provide us with all the answers, or, rather, the solutions, we are looking for and need. For this reason, miRNAs should be studied above all from the systems biology perspective, whereby the nonlinear interactions inherent in the multiple biomolecular components that make up the cell can be appreciated and taken into account. To do this, most, if not all, of the components of a given subsystem and its regulatory networks would probably need to be characterized.4 In this way, we can better understand how pathways and regulatory networks interconnect, how they develop and evolve temporally, and how they are involved in pathogenesis. The importance …