MicroRNAs and cancer: what we know and what we still have to learn

A report on the Keystone Symposia on MicroRNAs and Cancer, Keystone, Colorado, USA, 10-15 June 2009

The Interaction Between Two Worlds: MicroRNAs and Toll-Like Receptors

MicroRNAs (miRNAs) are critical mediators of posttranscriptional regulation via their targeting of the imperfect antisense complementary regions of coding and non-coding transcripts. Recently, researchers have shown that miRNAs play roles in many aspects of regulation of immune cell function by targeting of inflammation-associated genes, including Toll-like receptors (TLRs). Besides this indirect regulatory role of miRNAs, they can also act as physiological ligands of specific TLRs and initiate the signaling cascade of immune response. In this review, we summarize the potential roles of miRNAs in regulation of TLR gene expression and TLR signaling, with a focus on the ability of miRNAs bind to TLRs

Genetic control of mammalian T-cell proliferation with a synthetic RNA regulatory system - illusion or reality?

Synthetic RNA-based regulatory systems are used to program higher-level biological functions that could be exploited, among many applications, for in vivo diagnostic and therapeutic applications. Chen and colleagues have recently reported a significant technological advance by producing an RNA modular device based on a hammerhead ribozyme and successfully tested its ability to control the proliferation of mammalian T lymphocytes. Like all exciting research, this work raises a lot of significant questions. How quickly will such knowledge be translated into clinical practice? How efficient will this system be in human clinical trials involving adaptive T-cell therapy? We discuss the possible advantages of using such new technologies for specific therapeutic applications

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

miR-142: A Master Regulator in Hematological Malignancies and Therapeutic Opportunities

MicroRNAs (miRNAs) are a type of non-coding RNA whose dysregulation is frequently associated with the onset and progression of human cancers. miR-142, an ultra-conserved miRNA with both active -3p and -5p mature strands and wide-ranging physiological targets, has been the subject of countless studies over the years. Due to its preferential expression in hematopoietic cells, miR-142 has been found to be associated with numerous types of lymphomas and leukemias. This review elucidates the multifaceted role of miR-142 in human physiology, its influence on hematopoiesis and hematopoietic cells, and its intriguing involvement in exosome-mediated miR-142 transport. Moreover, we offer a comprehensive exploration of the genetic and molecular landscape of the miR-142 genomic locus, highlighting its mutations and dysregulation within hematological malignancies. Finally, we discuss potential avenues for harnessing the therapeutic potential of miR-142 in the context of hematological malignancies

Multiple Omics Levels of Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy characterized by the proliferation of functionally mature but incompetent B cells. It is the most prevalent type of leukemia in Western populations, accounting for approximately 25% of new leukemia cases. While recent advances, such as ibrutinib and venetoclax treatment have improved patient outlook, aggressive forms of CLL such as Richter transformation still pose a significant challenge. This discrepancy may be due to the heterogeneity of factors contributing to CLL development at multiple -omics levels. However, information on the omics of CLL is fragmented, hindering multi-omics-based research into potential treatment options. To address this, we aggregated and presented a selection of important aspects of various omics levels of the disease in this review. The purpose of the present literature analysis is to portray examples of CLL studies from different omics levels, including genomics, epigenomics, transcriptomics, epitranscriptomics, proteomics, epiproteomics, metabolomics, glycomics and lipidomics, as well as those identified by multi-omics approaches. The review includes the list of 102 CLL-associated genes with relevant genomics information. While single-omics studies yield substantial and useful data, they omit a significant level of complex biological interplay present in the disease. As multi-omics studies integrate several different layers of data, they may be better suited for complex diseases such as CLL and have thus far yielded promising results. Future multi-omics studies may assist clinicians in improved treatment choices based on CLL subtypes as well as allow the identification of novel biomarkers and targets for treatments

Ultraconserved Enhancers Roles in Cancer

https://openworks.mdanderson.org/sumexp21/1164/thumbnail.jp

The Genomic and Transcriptomic Landscape of Ultra-Conserved miR-142 in Hematological Malignancies

Department of Translational Molecular Pathology Department of Experimental Therapeutics Department of Translational Molecular Pathology, Department of Experimental Therapeutics, Center for RNA Interference and Non-Coding RNAs, Department of Leukemia, Division of Cancer Medicinehttps://openworks.mdanderson.org/sumexp22/1053/thumbnail.jp