MicroRNA history : discovery, recent applications and next frontiers

We thank the Department of Scientific Publications at The University of Texas MD Anderson Cancer Center for English language editing of the manuscript.Since 1993, when the first small non-coding RNA was identified, our knowledge about microRNAs has grown exponentially. In this review, we focus on the main progress in this field and discuss the most important findings under a historical perspective. In addition, we examine microRNAs as markers ofdisease diagnosis and prognosis, and as new therapeutic targets.M.I.A is supported by a PhD fellowship (SFRH/BD/47031/2008) from FCT (Fundação para a Ciência e Tecnologia) from Portugal. G.A.C. is supported as a Fellow at The University of Texas MD Anderson Research Trust, as a Fellow of The University of Texas System Regents Research Scholar, and by the CLL Global Research Foundation. Work in Dr. Calin’s laboratory was supported in part by NIH, by DoD, by 2009 Seena Magowitz – Pancreatic Cancer Action Network – AACR Pilot Grant and by the U.S./European Alliance for the Therapy of CLL

MicroRNAs and metastases--the neuroblastoma link

[Excerpt] MicroRNAs (miRNAs) are small noncoding RNAs of approximately 22 nucleotides in length that regulate gene expression post-transcriptionally. These small RNAs are fundamental regulators of several cellular processes, such as differentiation, development, apoptosis, proliferation, cell cycle regulation and metabolism, through the binding to 3' untranslated regions, coding sequence or 5' untranslated regions of target messenger RNAs (mRNAs), preventing their translation or causing their degradation.1 A modest change in only one miRNA will affect multiple mRNA targets; consequently, the deregulation of miRNAs has important consequences to the cellular homeostatic stability, and aberrant miRNAs expression patterns have been described in several types of cancer.2 Recently, miRNAs have been implicated in the metastatic process of several tumors such as human breast and colorectal cancers3 and, as reported this issue of Cancer Biology & Therapy by Guo et al. in neuroblastoma.4 These are extracranial solid tumors, arising from neural crest cells, that are most common in infants and children; metastasis, the main cause of death, is present at the time of diagnosis in approximately 60% of patients. (5) [...

The Many Faces of Long Noncoding RNAs in Cancer

SIGNIFICANCE: The emerging connections between an increasing number of long noncoding RNAs (lncRNAs) and oncogenic hallmarks provide a new twist to tumor complexity. Recent Advances: In the present review, we highlight specific lncRNAs that have been studied in relation to tumorigenesis, either as participants in the neoplastic process or as markers of pathway activity or drug response. These transcripts are typically deregulated by oncogenic or tumor-suppressing signals or respond to microenvironmental conditions such as hypoxia. CRITICAL ISSUES: Among these transcripts are lncRNAs sufficiently divergent between mouse and human genomes that may contribute to biological differences between species. FUTURE DIRECTIONS: From a translational standpoint, knowledge about primate-specific lncRNAs may help explain the reason behind the failure to reproduce the results from mouse cancer models in human cell-based systems. Antioxid. Redox Signal. 29, 922-935

Giant thermal expansion and α-precipitation pathways in Ti-Alloys

Ti-Alloys represent the principal structural materials in both aerospace development and metallic biomaterials. Key to optimizing their mechanical and functional behaviour is in-depth know-how of their phases and the complex interplay of diffusive vs. displacive phase transformations to permit the tailoring of intricate microstructures across a wide spectrum of configurations. Here, we report on structural changes and phase transformations of Ti-Nb alloys during heating by in situ synchrotron diffraction. These materials exhibit anisotropic thermal expansion yielding some of the largest linear expansion coefficients (+ 163.9×10-6 to-95.1×10-6 °C-1) ever reported. Moreover, we describe two pathways leading to the precipitation of the α-phase mediated by diffusion-based orthorhombic structures, α″lean and α″iso. Via coupling the lattice parameters to composition both phases evolve into α through rejection of Nb. These findings have the potential to promote new microstructural design approaches for Ti-Nb alloys and β-stabilized Ti-Alloys in general

Lagrangian Variational Framework for Boundary Value Problems

A boundary value problem is commonly associated with constraints imposed on a system at its boundary. We advance here an alternative point of view treating the system as interacting "boundary" and "interior" subsystems. This view is implemented through a Lagrangian framework that allows to account for (i) a variety of forces including dissipative acting at the boundary; (ii) a multitude of features of interactions between the boundary and the interior fields when the boundary fields may differ from the boundary limit of the interior fields; (iii) detailed pictures of the energy distribution and its flow; (iv) linear and nonlinear effects. We provide a number of elucidating examples of the structured boundary and its interactions with the system interior. We also show that the proposed approach covers the well known boundary value problems.Comment: 41 pages, 3 figure

Chronic lymphocytic leukemia: interplay between noncoding RNAs and protein-coding genes

One of the most unexpected and fascinating discoveries in oncology over the past few years is the interplay between abnormalities in protein-coding genes and noncoding RNAs (ncRNAs) that is causally involved in cancer initiation, progression, and dissemination. MicroRNA