Carlos Stahlhut

MicroRNAs (miRNAs) have emerged as key genetic regulators of a wide variety of biological processes, including growth, proliferation, and survival. Recent advances have led to the recognition that miRNAs can act as potent oncogenes and tumor suppressors, playing crucial roles in the initiation, maintenance, and progression of the oncogenic state in a variety of cancers. Determining how miRNA expression and function is altered in cancer is an important goal, and a necessary prerequisite to the development and adoption of miRNA-based therapeutics in the clinic. Highly promising clinical applications of miRNAs are the use of miRNA signatures as biomarkers for cancer (for example, for early detection or diagnosis), and therapeutic supplementation or inhibition of specific miRNAs to alter the cancer phenotype. In this review, we discuss the main methods used for miRNA profiling, and examine key miRNAs that are commonly altered in a variety of tumors. Current studies underscore the functional versatility and potency of miRNAs in various aspects of the cancer phenotype, pointing to their potential clinical applications. Consequently, we discuss the application of miRNAs as biomarkers, clinical agents, and therapeutic targets, highlighting both the enormous potential and major challenges in this field.

microRNAs (miRNAs) represent approximately 4% of the genes in vertebrates, where they regulate deadenylation, translation, and decay of the target messenger RNAs (mRNAs). The integrated role of miRNAs to regulate gene expression and cell function remains largely unknown. Therefore, to identify the targets coordinately regulated by muscle miRNAs in vivo, we performed gene expression arrays on muscle cells sorted from wild type, dicer mutants, and single miRNA knockdown embryos. Our analysis reveals that two particular miRNAs, miR-1 and miR-133, influence gene expression patterns in the zebrafish embryo where they account for >54% of the miRNA-mediated regulation in the muscle. We also found that muscle miRNA targets (1) tend to be expressed at low levels in wild-type muscle but are more highly expressed in dicer mutant muscle, and (2) are enriched for actin-related and actin-binding proteins. Loss of dicer function or down-regulation of miR-1 and miR-133 alters muscle gene expression and disrupts actin organization during sarcomere assembly. These results suggest that miR-1 and miR-133 actively shape gene expression patterns in muscle tissue, where they regulate sarcomeric actin organization.

Cancer is a complex and dynamic disease, involving a variety of changes in gene expression and structure. Traditionally, the study of cancer has focused on protein-coding genes, considering these as the principal effectors and regulators of tumorigenesis. Recent advances, however, have brought non-protein-coding RNA into the spotlight. MicroRNAs (miRNAs), one such class of non-coding RNAs, have been implicated in the regulation of cell growth, differentiation, and apoptosis [1]. While their study is still at an early stage, and their mechanism of action along with their importance in cancer is not yet fully understood, they may provide an important layer of genetic regulation in tumorigenesis, and ultimately become valuable therapeutic tools.