Field Of miRNA Biology Research Articles

MicroRNA therapeutics: towards a new era for the management of cancer and other diseases.

In just over two decades since the discovery of the first microRNA (miRNA), the field of miRNA biology has expanded considerably. Insights into the roles of miRNAs in development and disease, particularly in cancer, have made miRNAs attractive tools and targets for novel therapeutic approaches. Functional studies have confirmed that miRNA dysregulation is causal in many cases of cancer, with miRNAs acting as tumour suppressors or oncogenes (oncomiRs), and miRNA mimics and molecules targeted at miRNAs (antimiRs) have shown promise in preclinical development. Several miRNA-targeted therapeutics have reached clinical development, including a mimic of the tumour suppressor miRNA miR-34, which reached phase I clinical trials for treating cancer, and antimiRs targeted at miR-122, which reached phase II trials for treating hepatitis. In this article, we describe recent advances in our understanding of miRNAs in cancer and in other diseases and provide an overview of current miRNA therapeutics in the clinic. We also discuss the challenge of identifying the most efficacious therapeutic candidates and provide a perspective on achieving safe and targeted delivery of miRNA therapeutics.

Discovering MicroRNAs and Their Targets in Plants

MicroRNAs (miRNAs) are a subset of endogenous approximate 22 nucleotide (nt), small non-coding regulatory RNA molecules that regulate gene expression post-transcriptionally by mediating mRNA degradation or translational repression in a sequence specific manner. Plant miRNA research gained momentum, 2002 onwards, which was accompanied by the discovery of plant proteins involved in miRNA biogenesis. Progress in genomic research of different plant species may open the door for discovering novel miRNAs and their characteristics. With the development and availability of experimental technologies and computational approaches, the field of miRNA biology has advanced tremendously over the last decade. This paper aims to introduce major computational approaches in the identification of plant miRNAs, including conservation based search, de novo prediction and mining in deep sequencing data. Computational tools for identification of miRNAs target is another intriguing perspective that has been examined in this review. All these approaches have certain advantages and disadvantages, which are reviewed in the present survey. Furthermore, in the present survey, we also present many experimental modalities such as Degradome sequencing, Immunoprecipitation of RISC components and their limitations for miRNAs targets identification. At the end, we also present the outlook for future directions in the development and improvement of plant miRNA discovery methods.

MicroRNAs as Developmental Regulators.

The field of miRNA biology is relatively young, but its impact on our understanding of the regulation of a wide array of cell functions is far-reaching. The importance of miRNAs in development has become nearly ubiquitous, with miRNAs contributing to development of most cells and organs. Although miRNAs are clearly interwoven into known regulatory networks that control cell development, the specific modalities by which they intersect are often quite distinct and cleverly achieved. The frequently emerging theme of feed-back and feed-forward loops to either counterbalance or reinforce the gene programs that they influence is a common thread. Many of these examples of miRNAs as developmental regulators are presently found in organs with different miRNAs and targets, whereas novel, unexpected themes emerge in the context of mouse development as we learn more about this rapidly developing area of biology.

Functions of MicroRNAs in Cardiovascular Biology and Disease

In 1993, lin-4 was discovered as a critical modulator of temporal development in Caenorhabditis elegans and, most notably, as the first in the class of small, single-stranded noncoding RNAs now defined as microRNAs (miRNAs). Another eight years elapsed before miRNA expression was detected in mammalian cells. Since then, explosive advancements in the field of miRNA biology have elucidated the basic mechanism of miRNA biogenesis, regulation, and gene-regulatory function. The discovery of this new class of small RNAs has augmented the complexity of gene-regulatory programs as well as the understanding of developmental and pathological processes in the cardiovascular system. Indeed, the contributions of miRNAs in cardiovascular development and function have been widely explored, revealing the extensive role of these small regulatory RNAs in cardiovascular physiology.

The Duality of OncomiR Addiction in the Maintenance and Treatment of Cancer

It has long been established that cancers can become addicted to particular oncogenes. Despite the genetic complexity that governs tumorigenesis, certain cancers can exhibit a critical dependency on the expression of a single oncogene, which when removed leads to death of the cancer cell. Recent observations on the relationships between regulatory RNAs and cancer have revealed that this concept of oncogene addiction extends to microRNAs (miRNAs) as well. Certain cancers exhibit a dependency on the expression of a single oncogenic miRNA, or oncomiR. The field of miRNA biology and its involvement in diseases such as cancer have seen tremendous advances over the past decade. However, little is known about the phenomenon of oncomiR addiction. In this review, we introduce the concept of proto-oncomiRs, or miRNAs that gain oncogenic activity after an initiating event. Furthermore, by highlighting the role of proto-oncomiRs in generating malignant phenotypes, we glean possible insights into the mechanisms that guide oncomiR addiction. In addition, toward the realization of genetically driven personalized medicine, some of the most clinically successful anticancer strategies have involved targeting addictive oncogenes such as HER2, BCR/ABL, EGFR, and VEGF. Elucidating how addictive miRNAs can perpetuate cancer may reveal additional critical molecular targets to exploit for therapeutic purposes. Therefore, in this review, we also summarize the field of anti-miRNA therapeutics, in which antisense and nanoscale delivery technologies are the driving force. Addictive oncomiRs are a double-edged sword; addicted cancers are dependent on oncomiRs that are highly potent therapeutic targets. Dissection of this phenomenon may reveal the mechanisms through which lynchpin miRNAs can perpetuate cancer and present a new paradigm for miRNA-based cancer therapy.

Genome‐wide approaches in the study of microRNA biology

MicroRNAs (miRNAs), a class of ∼21-23 nucleotide long non-coding RNAs (ncRNAs), have critical roles in diverse biological processes that encompass development, proliferation, apoptosis, stress response, and fat metabolism. miRNAs recognize their target mRNA transcripts by partial sequence complementarity and collectively have been estimated to regulate the majority of human genes. Consequently, misregulation of miRNAs or disruption of their target sites in genes has been implicated in a variety of human diseases ranging from cancer metastasis to neurological disorders. With the development and availability of genomic technologies and computational approaches, the field of miRNA biology has advanced tremendously over the last decade. Here we review the genome-wide approaches that have allowed for the discovery of new miRNAs, the characterization of their targets, and a systems-level view of their impact.

Clinical Applications of Mirnas in Cardiac Remodeling and Heart Failure

MicroRNAs (miRNAs or miRs) are short, highly conserved noncoding RNAs that regulate gene expression at the post-transcriptional level by inhibiting translation or promoting the degradation of target mRNA. Even though the field of miRNA biology is relatively young, growing lines of evidence suggest that miRNAs play a key role pathogenesis of heart failure through their ability to regulate genes that govern the process of adaptive and maladaptive cardiac remodeling. Herein, we review the biology of miRNAs in relation to their role in modulating various aspects of the cardiac remodeling process, as well as discuss the potential applications of miRNA biology to the field of heart failure.

The Emerging Role of MicroRNAs in Cardiac Remodeling and Heart Failure

Recent studies have suggested a potentially important role for a family of tiny regulatory RNAs, known as microRNAs (miRNAs or miRs), in the control of diverse aspects of cardiac function in health and disease. Although the field of miRNA biology is relatively new, there is emerging evidence that miRNAs may play an important role in the pathogenesis of heart failure through their ability to regulate the expression levels of genes that govern the process of adaptive and maladaptive cardiac remodeling. Here, we review the biology of miRNAs in relation to their role in modulating various aspects of the process of cardiac remodeling, as well as discuss the potential application of miRNA biology to the field of heart failure.