Issue No. 11, November 2017
VCU Institute of Molecular Medicine (VIMM) NEWS & VIEWS
The VIMM, established in 2008 by Paul B. Fisher, M.Ph., Ph.D., the Founding Director, is comprised of outstanding scientists/clinicians from VCU School of Medicine focusing on important medical-related research in cancer, neurodegeneration and infectious diseases. The purpose of this NEWS & VIEWS is to highlight the exciting research being performed by the VIMM members.     
miRNA and Cancer

  • Research in the past 10 years has established miRNA, a small noncoding RNA, as a key contributor of diverse biochemical and cellular functions.

  • Researchers have also demonstrated that dysregulation of microRNAs occurs in and contributes to all types of cancer.

  • Deregulated miRNAs can be used as a tool for the diagnosis, prognosis, and monitoring of human cancer.

  • MicroRNAs could be used as therapies for malignancies that depend on their loss for transformation, and antimicroRNAs could be therapeutic for malignancies caused by overexpression of microRNAs.

  • A thematic volume in Advances in Cancer Research edited by Drs. Carlo M. Croce and Paul B. Fisher summarizes recent exciting developments in many aspects of microRNA biology and in defining the role of microRNA in disease, and of the use of microRNA dysregulation for the diagnosis, prognosis, and monitoring of cancer. The volume can be found at https://www.sciencedirect.com/science/bookseries/0065230X/135
               Paul B. Fisher, M.Ph., Ph.D.
               VCU Institute of Molecular Medicine
               VCU Massey Cancer Center
               Virginia Commonwealth University
               School of Medicine
               Richmond, VA, USA
Carlo M. Croce, M.D.
Professor and Chair
Dept. of Cancer Biology and Genetics
Wexner Medical Center
The Ohio State University
Columbus, OH, USA
Chapter 1 provides a historical perspective on the discovery and development of miRNA (Drusco and Croce: MicroRNAs and Cancer: A Long Story for Short RNAs). Specifically, the chapter summarizes the discovery of microRNAs from C. elegans to their debut in cancer and medicine, the concurrent development of technologies, and future translational applications. Despite challenges in the development of microRNAs as drugs, technologies and computational approaches are continuously being improved to fulfill the microRNA potential.

Chapter 2 (The Enigma of miRNA Regulation in Cancer: Anjan K. Pradhan, Luni Emdad, Swadesh K. Das, Devanand Sarkar, and Paul B. Fisher) discusses upstream regulatory molecules of miRNAs. Particularly in this chapter, Pradhan et al. summarize the upstream controlling molecules that influence miRNA with a focus on the factors and processes involved in miRNA regulation.

Animal models are invaluable tools to assess the role of genes in cancer, and animal models carrying dysregulated microRNA genes have been developed and have provided important validations for their role in cancer pathogenesis. In Chapter 3 (Animal Models to Study MicroRNA Function) Pal and Kasinski provide an overview of the important contributions made in the microRNA field using model organisms. Specifically, this chapter highlights the various strategies used to generate transgenic organisms and a critical review of the use of transgenic mice for evaluating preclinical efficacy of microRNA-based cancer therapeutics.

Chapter 4 (VanRoosbroeck and Calin: Cancer Hallmarks and MicroRNAs: The Therapeutic Connection) provides a review of current therapeutics focused on miRNA-protein targets. Particularly, the authors describe the involvement of miRNAs in cancer from a cancer hallmarks and targeted therapeutics point of view with a focus on protein-coding miRNA targets for which targeted therapeutics in oncology are already approved by the FDA.

In Chapter 5 (Ryan: microRNAs in Cancer Susceptibility) the author discusses some of the recent advances in miRNA-Single Nucleotide Polymorphism (SNP) literature—including SNPs in miRNA genes, miRNA binding sites, and miRNA biogenesis and processing. The author also highlights some emerging areas of interest, including isomiRs and non-3’UTR focused miRNA-binding mechanisms that could provide further novel insight into the relationship between miR-SNPs and cancer.

Chapter 6 (Role of the tRNA-Derived Small RNAs in Cancer: New Potential Biomarkers and Target for Therapy: Veronica Balatti, Yuri Pekarsky, and Carlo M. Croce) discusses the role of tRNA-derived small RNAs (tsRNAs) in cancer by regulating gene expression. The authors emphasize that tsRNAs can be considered unique sequences and are able to bind both Argonaute proteins (like miRNAs) and Piwi proteins (like piRNAs), their dysregulation could play a critical role in cancer by interfering with the regulation gene expression at various diverse levels.

Chapter 7 (MicroRNAs and Epigenetics: Catia Moutinho and Manel Esteller) discusses the role of epigenetics in the regulation of miRNA expression. Specifically, the authors discuss the supportive links between miRNAs and epigenetics in the context of carcinogenesis, and emphasize that miRNAs can be epigenetically regulated by DNA methylation and/or specific histone modifications.

Publication: Advances in Cancer Research Volume 135, Pages 1-220 (2017). miRNA and Cancer. Edited by Carlo M. Croce and Paul B. Fisher.

Figure legend: Utility of model systems in various aspects of miRNA research. The model systems highlighted in this review include C. elegans (worms), D. melanogaster (flies), D. rerio (fish), and M. musculus (mice). All the enlisted model systems have contributed immensely toward the identification of evolutionarily conserved miRNAs and delineating their mechanism of action in normal cells. The simple organisms, worms and flies, do not develop cancers; hence, they have mainly been utilized to delineate miRNA biogenesis and function. However, the more complex systems, fish and mice, with an intact immune and angiogenic system have shown immense robustness in identifying the normal functions of miRNAs, and their roles in driving tumorigenesis. Since the discovery of the first miRNA, lin-4, in 1993, these in vivo systems have come a long way and have demonstrated their applicability as preclinical model organisms to predict therapeutic relevance of certain miRNAs. Illustration created using graphics from Library of Science & Medical Illustrations ( http://www.somersault1824.com/science-illustrations/) and Server Medical Art ( http://www.servier.fr /servier-medical-art).
Contributors in this volume : Veronica Balatti, Alessandra Drusco, Yuri Pekarsky and Carlo M. Croce are from The Ohio State University, Columbus, OH, USA. George A. Calin and Katrien Van Roosbroeck are from The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Anjan K. Pradhan, Luni Emdad, Swadesh K. Das, Devanand Sarkar, and Paul B. Fisher are from Virginia Commonwealth University, School of Medicine, Richmond, VA, USA. Arpita S. Pal and Andrea L. Kasinski are from Purdue University, West Lafayette, IN, USA. Bríd M. Ryan is from Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. Manel Esteller and Catia Moutinho are from the Cancer Epigenetics and Biology Program, University of Barcelona, Catalonia, Spain.